Book - Physiology of the Fetus 10: Difference between revisions

From Embryology
Line 6: Line 6:
=Chapter X The Genesis of Function in the Nervous System=
=Chapter X The Genesis of Function in the Nervous System=


THE beginning of functional activity in the nervous system has
THE beginning of functional activity in the nervous system has been investigated most thoroughly in embryos of the rat,I-4 guinea pig,5- S sheepfs 8 and cat,9-13 and less completely in man14s 15 and other mammals.10-I7 studies in the lower vertebrates,18-22 especially amphibia, have influenced conceptions of behavioral de— velopment in mammals to a very considerable extent. A complete review of all articles on the subject of early fetal movements would require far more space than is available in the present chapter.
been investigated most thoroughly in embryos of the rat,I-4 guinea
pig,5- S sheepfs 8 and cat,9-13 and less completely in man14s 15 and
other mammals.10-I7 studies in the lower vertebrates,18-22 especially amphibia, have influenced conceptions of behavioral de—
velopment in mammals to a very considerable extent. A complete
review of all articles on the subject of early fetal movements
would require far more space than is available in the present chap—
tclc


A B C


Fig. 47.—Embryo.s of the (.-1) rat, (B) cat and (C) human at approximately
the stage in development at which simple rellexes are expected for the first time.
crownckump length: 12 mm. rat; 14 mm. cat; 18 mm. human (7 weeks) . Magni—
ficatiom X Z.


1t is impossible to say precisely when nerve cells attain the
ability to discharge or when kibers can conduct nervous impulses
for the first time. However, muscle contractions induced by
nervous activity can be elicited surprisingly early in prenatal life.
The stage at which nervous function is first observable in mammals varies to some extent, but in all species that have been in—


138
Fig. 47. Embryos of the (A) rat, (B) cat and (C) human at approximately the stage in development at which simple rellexes are expected for the first time. crownckump length: 12 mm. rat; 14 mm. cat; 18 mm. human (7 weeks). Magnificatiom X Z.
oENEs1s or FUNCTION IN NEnvoUs sYsTEM 139


vestigated it is before body form has talcen on the characteristic
appearance of the species. In other words, somatic movements
start before the close of the embryonic, rather than in the fetal
period. This is illustrated by the accompanying photographs of
rat, cat and human embryos talcen at about the time simple reHexes can first be induced (Fig. 47) .


The initiation of function in slceletal muscle cells was considered in the preceding chapten Myogenic xesponses precede
1t is impossible to say precisely when nerve cells attain the ability to discharge or when kibers can conduct nervous impulses for the first time. However, muscle contractions induced by nervous activity can be elicited surprisingly early in prenatal life. The stage at which nervous function is first observable in mammals varies to some extent, but in all species that have been investigated it is before body form has talcen on the characteristic appearance of the species. In other words, somatic movements start before the close of the embryonic, rather than in the fetal period. This is illustrated by the accompanying photographs of rat, cat and human embryos talcen at about the time simple reHexes can first be induced (Fig. 47) .
reiiexes by at least one day in most mamma1s. The development
of muscle iibers and of motor nerves with simple epilemmal motor
nerve endings goes hand -in hand, but there does not seem to be
an immediate correlation between the appearance of motor end—
ings and Csunctional reflexes as some have suggestedks From the
structural point of view it is possible that muscle contractions can
be induced by discharge of motor neurons before reflex arcs have
been completely formed. With the advent of conduction from
afferent to efkerent neurons through synaptic centers, reHex re—
sponses to stimulation are manifested. At this point in deve1opment behavior may be said to have its genesis.


MYOGENIC RESPONSES


Let us examine the antecedents of behavioral genesis in somewhat gyeater detail. spontaneous muscle twitching characterizes
The initiation of function in slceletal muscle cells was considered in the preceding chapten Myogenic xesponses precede reiiexes by at least one day in most mamma1s. The development of muscle iibers and of motor nerves with simple epilemmal motor nerve endings goes hand -in hand, but there does not seem to be an immediate correlation between the appearance of motor end— ings and Csunctional reflexes as some have suggestedks From the structural point of view it is possible that muscle contractions can be induced by discharge of motor neurons before reflex arcs have been completely formed. With the advent of conduction from afferent to efkerent neurons through synaptic centers, reHex re— sponses to stimulation are manifested. At this point in deve1opment behavior may be said to have its genesis.
embryos of certain lower vertebrates before reHex excitation becomes eifective. 0bservations in fishes are especially notable.I9
The similarity to spontaneous contractions of myob1asts and
muscle iibers in cultures of embryonic chiclc tissues is striking. It
is possible that some of the earliest spontaneous movements »observed in the intact living chick embryo1S-21-24-25 are of this natake. ·


No comparable phenomenon has been seen in .mammalian
==Myogenic Responses==
embryos studied under normal« physiologic conditions. However,
the movements which manifest themselves in ionically unbalanced
saline solutions probably are myogenic responsesKs Why spontaneous muscle twitching is not encountered normally in mammalian embryos has not been determined. Musculature is laid
down well in advance of- the time it can be activated reflexly in
the rat, guinea pig, sheep and cat.


Mechanical and electrical stimuli applied directly to muscle
Let us examine the antecedents of behavioral genesis in somewhat gyeater detail. spontaneous muscle twitching characterizes embryos of certain lower vertebrates before reHex excitation becomes eifective. 0bservations in fishes are especially notable.I9 The similarity to spontaneous contractions of myob1asts and muscle iibers in cultures of embryonic chiclc tissues is striking. It is possible that some of the earliest spontaneous movements »observed in the intact living chick embryo1S-21-24-25 are of this nature.
140 PHYSIOLOGY OF THE FETUs·


masses of intact embryoX efkect contractions readily. Microselecs
trodes constructed of Hne nichrome wires insulated except at the
tips serve admirably for deliveringdocalized faradic shoclcs. Contractions of the embryonic slceletal muscles induced in this manner possess certain characteristics which distinguish them from
other types of somatic movement. They are as follows: (a) a
minimal stimulus, just adequate to produce a response, gives rise
to a quiclc contraction followed by a slower relaxationx (b) each
succeeding stimulation produces a similar contraction, for there
is no noticeable interval of fatigue during which the muscle is re—
fractoryz (c) the contraction is remarlcably well localized in a
small region immediately around the tips of the electrodes and
consequently -movements in several planes can usually be brought
about by shifting the Position of the electrodes; (d) the embryonic muscle tissue retains a high degree of excitability irrespective of great changes in metabolic conditions. In fact, specimens which have been allowed to bleed until white, which have
cooled to room temperature and in which the heart has practically
stopped beating still respond to direct stimulation of the slceletal
musculature. «


All the muscles of an embryo do not simultaneously reach a
No comparable phenomenon has been seen in .mammalian embryos studied under normal physiologic conditions. However, the movements which manifest themselves in ionically unbalanced saline solutions probably are myogenic responsesKs Why spontaneous muscle twitching is not encountered normally in mammalian embryos has not been determined. Musculature is laid down well in advance of the time it can be activated reflexly in the rat, guinea pig, sheep and cat.
state of development in which contractions are possible. The
first in which such direct responses can be observed are those ok
the forelimbs at the attachment to the body. With advancement
of growth,.excitability spreads both rostrally and caudally as well
as distally from these po»ints.


NEUROMOTOR RESPONSES


The second step in development of behavior is thought to be
Mechanical and electrical stimuli applied directly to muscle masses of intact embryoX efkect contractions readily. Microselecs trodes constructed of Hne nichrome wires insulated except at the tips serve admirably for deliveringdocalized faradic shoclcs. Contractions of the embryonic slceletal muscles induced in this manner possess certain characteristics which distinguish them from other types of somatic movement. They are as follows: (a) a minimal stimulus, just adequate to produce a response, gives rise to a quiclc contraction followed by a slower relaxationx (b) each succeeding stimulation produces a similar contraction, for there is no noticeable interval of fatigue during which the muscle is re— fractoryz (c) the contraction is remarlcably well localized in a small region immediately around the tips of the electrodes and consequently -movements in several planes can usually be brought about by shifting the Position of the electrodes; (d) the embryonic muscle tissue retains a high degree of excitability irrespective of great changes in metabolic conditions. In fact, specimens which have been allowed to bleed until white, which have cooled to room temperature and in which the heart has practically stopped beating still respond to direct stimulation of the slceletal musculature.
the appearance of muscle contraction in response to. excitation of
motor neurons.27 Nerve endings of a primitive lcind (Fig. 45)
are present upon developing muscle übers at a time when the
only somatic movements are those which follow direct skimulation
of the muscleskss 29 Although it has been impossible to obtain
direct evidence in the youngest cat embryos that purely neuromuscular contractions precede rellexes, such contractions can be
demonstrated in specimens a little more advanced, in which reflex
responses are already obtainable. After the reflexes have died
away with deterioration of the· plsysiologic oonditions of the
cENEsIs OF kUNcTlcN IN NERVOUS sYsTEM 141


embryo, stimulation of motor centers produces movements. A
s1ender and sharp dental broach was used to pierce the tissues of
the back and the spinal cord of the embryos. It was found that
a baclcward movement of the forelimb followed when the instrument was passed into the spinal cord at the level between C.7
and T.1 and a forward movement resulted in the same specimens
when it was inserted at the level between c.4 and c.6. The true
reflexes which had been obtained previously were all baclcward
and outward movements of the 1imbs. Thus it is apparent that a
new forward movement of the arm had been induced by direct
stimulation of a motor center before such a movement occurred
as the result of retlex stimulation of afferent nerves. It is especially noteworthy that the responses were localized and that there
was no diffuse spreading of excitation through the center even
with this rather crude form of stimulation. The segmentaL nonintegrated character of the motor ce11 column of the embryonic
spinal cord, so clearly evident in silver-stained histologic preparations, is demonstrable by physiologic methods.


GENESIS OF REFLEX BEEAVIOR
All the muscles of an embryo do not simultaneously reach a state of development in which contractions are possible. The first in which such direct responses can be observed are those ok the forelimbs at the attachment to the body. With advancement of growth,.excitability spreads both rostrally and caudally as well as distally from these points.


The third step in behavioral development is characterized by
==Neuromotor Responses==
the appearance of reflexes. These do not manifest themselves
unti1 atkerent and efferent neurons, simple nerve endings in
peripheral tissues, connector neurons in the central nervous system and functional synaptic central mechanisms have been
formed. ·


There are essentially two conceptions of the development of
The second step in development of behavior is thought to be the appearance of muscle contraction in response to. excitation of motor neurons.27 Nerve endings of a primitive lcind (Fig. 45) are present upon developing muscle übers at a time when the only somatic movements are those which follow direct skimulation of the muscleskss 29 Although it has been impossible to obtain direct evidence in the youngest cat embryos that purely neuromuscular contractions precede rellexes, such contractions can be demonstrated in specimens a little more advanced, in which reflex responses are already obtainable. After the reflexes have died away with deterioration of the· physiologic oonditions of the embryo, stimulation of motor centers produces movements. A s1ender and sharp dental broach was used to pierce the tissues of the back and the spinal cord of the embryos. It was found that a backward movement of the forelimb followed when the instrument was passed into the spinal cord at the level between C.7 and T.1 and a forward movement resulted in the same specimens when it was inserted at the level between c.4 and c.6. The true reflexes which had been obtained previously were all baclcward and outward movements of the 1imbs. Thus it is apparent that a new forward movement of the arm had been induced by direct stimulation of a motor center before such a movement occurred as the result of retlex stimulation of afferent nerves. It is especially noteworthy that the responses were localized and that there was no diffuse spreading of excitation through the center even with this rather crude form of stimulation. The segmentaL nonintegrated character of the motor ce11 column of the embryonic spinal cord, so clearly evident in silver-stained histologic preparations, is demonstrable by physiologic methods.
behavior in mammalian embryos. 0ne group of investigatorsY
II· IS believe that they have demonstrated the genesis of reflexes
by a process of individuation from a fully integrated mass reaction or «total Patter·n." In other words, they believe that more
or less discrete movements are not the primary units of behavior
but that local reflexes difkerentiate from a more fundamental
baclcground of massive movement. Another group of investigatorsws 30 hold the opposjng view that the basic elements in the
genesis of mammalian behavior are relatively simple reliex re—
sponses. They lind that the more complex reactions of older
fetuses are formed by progressive neuronal integration of the less
complicated activities of the embryo. some other investigatorss
142 PHYSIOLOGY OF THE FETUS


maintain that both theories are partially true, but are inclined to
kavor the form-er.


THE CONCEPT OF Ä TOTAL PATTERN
==Genesis Of Reflex Behavior==


The doctrine of development of behavior from a total pattern
The third step in behavioral development is characterized by the appearance of reflexes. These do not manifest themselves unti1 atkerent and efferent neurons, simple nerve endings in peripheral tissues, connector neurons in the central nervous system and functional synaptic central mechanisms have been formed.
is based on a long series of correlated physiologic and histologic
studies by coghill in the urode1e amphibiam Amblystoma, ap—
pearing frequently since 1913 and summarized in his London lec
x Ifloor PMB cslls


Fig. 48.—Diagram of the sensoryimotor mechanism of the Salamander embryo


which acoounts for the cephalwcaudal progkession of movement away from the
There are essentially two conceptions of the development of behavior in mammalian embryos. 0ne group of investigatorsY II· IS believe that they have demonstrated the genesis of reflexes by a process of individuation from a fully integrated mass reaction or «total Patter·n." In other words, they believe that more or less discrete movements are not the primary units of behavior but that local reflexes difkerentiate from a more fundamental baclcground of massive movement. Another group of investigatorsws 30 hold the opposjng view that the basic elements in the genesis of mammalian behavior are relatively simple reliex re— sponses. They lind that the more complex reactions of older fetuses are formed by progressive neuronal integration of the less complicated activities of the embryo. some other investigators 2 maintain that both theories are partially true, but are inclined to kavor the former.
side stimulated Arrows indicate direction of conductiom (coghi11: «Anatomy and


the Problem of Behavior," Cambridge Unim Press.)
==The Concept of a Total Pattern==


turesEs It was found that a motor mechanism develops on either
The doctrine of development of behavior from a total pattern is based on a long series of correlated physiologic and histologic studies by coghill in the urode1e amphibiam Amblystoma, ap— pearing frequently since 1913 and summarized in his London lectures.  18 It was found that a motor mechanism develops on either side of the embryonic floor plate as a longitudinally conducting system of neurons. Each neuron extends a process caudally to the next one; from this Process branches run to the muscles of the baclc and later to the 1imbs. Thesseries of neurons constitutes an integrating motor system which is laid down before kunction appears. An integrating s«ensory system is kormed by temporary neurons, the Rohon-Beard ce11s in the dorsal portion ok the spinal cord. They too send out processes, but in a rostral direction, with branches running to the epithelium and the muscles. The motor and sensory systems become connected by commissural fioorplate neurons, appearing iirst near the rostral end ok the embryo. These relations are illustrated in Figs. 48 and 49.
side of the embryonic floor plate as a longitudinally conducting
system of neurons. Each neuron extends a process caudally to
the next one; from this Process branches run to the muscles of the
baclc and later to the 1imbs. Thesseries of neurons constitutes an
oENEsrs or FUNoHoN 1N NEnvoUs sYsTEM 143


integrating motor system which is laid down before kunction appears. An integrating s«ensory system is kormed by temporary
neurons, the Rohon-Beard ce11s in the dorsal portion ok the spinal
cord. They too send out processes, but in a rostral direction, with
branches running to the epithelium and the muscles. The motor
and sensory systems become connected by commissural fioovplate


Spinoi cord
-(-—«-’——


 


T Gkk Moses· Post)
· —0 s» Riqht mofor YOU«


Xsksoor Plds cell
'''Fig. 48.''' Diagram of the sensoryimotor mechanism of the Salamander embryo which acoounts for the cephalwcaudal progkession of movement away from the side stimulated Arrows indicate direction of conductiom (Coghi11: "Anatomy and the Problem of Behavior," Cambridge Univ. Press.)


Fig. 49.—Diagrarn ok the neuromotor mechanism ok the Salamander embryo
which allows an initial irnpulse (a, w) to be kollowed by a oontralatetal secondary
Impulse (c, X) through an intermediate connecting neuron (b) . This makes pos—
sible the swimming rnovernents like those in Fig. He. (coghi11: «Anatomy and the
Problem ok Behavior," cambridge Univ. Press.)


neurons, appearing iirst near the rostral end ok the embryo.
These relations are illustrated in Figs. 48 and 49.


A stimulus which is applied to one side of the embryonic
'''Fig. 49.''' Diagram of the neuromotor mechanism ok the Salamander embryo which allows an initial irnpulse (a, w) to be kollowed by a oontralatetal secondary Impulse (c, X) through an intermediate connecting neuron (b) . This makes pos— sible the swimming rnovernents like those in Fig. He. (coghi11: «Anatomy and the Problem ok Behavior," cambridge Univ. Press.)
salamander sets up impulses which are conducted rostra11y in the
sensory System, across the· kloopplate neurons near its rostral end,
and then caudally in the integrating motor System. contralateral flexion is thereupon the iirst true» behavioral responsez it«
144 Pktysxoxock oF THE FETUs


is a mass movement or fully integrated response ’from the very
start. This reaction is iliustrated in a series of drawings taken
from a motion-picture record« (Fig. Ho) . The single flexion
stage is followed shortly by bilateral ilexion and then by typical
swimming. The latter depends upon the appearance of collateral branches of motor neurons (Fig. 49) which allow the
caudal1y flowing impulses of one side ·to precede those of the


Fig. 5o.-seria1 tracings from motion pictures (frame numhers indicatety of
the earliest contralateral movement in response to stimulation of a Salamander
embryo. The neural mechanism involved is illustrated in Fig. 48. (coghill:


«Anatomy and the Problem of Behavior," cambridge Univ. Press.)
A stimulus which is applied to one side of the embryonic salamander sets up impulses which are conducted rostra11y in the sensory System, across the· kloopplate neurons near its rostral end, and then caudally in the integrating motor System. contralateral flexion is thereupon the iirst true» behavioral responsez it is a mass movement or fully integrated response ’from the very start. This reaction is iliustrated in a series of drawings taken from a motion-picture record« (Fig. Ho) . The single flexion stage is followed shortly by bilateral ilexion and then by typical swimming. The latter depends upon the appearance of collateral branches of motor neurons (Fig. 49) which allow the caudal1y flowing impulses of one side ·to precede those of the other. In this way two waves of movement can course down the trunlc as shown in Figs. 51 and 52. 0ne response coming upon another in this manner produces forward propulsion of the embryo, establishing aquatic locomotion.


other. In this way two waves of movement can course down the
trunlc as shown in Figs. 51 and 52. 0ne response coming upon


·another in this manner produces forward propulsion of the


embryo, establishing aquatic locomotion.


Later, as the 1imbs grow out they first move with the trunlc
Fig. 50. Serial tracings from motion pictures (frame numhers indicatety of the earliest contralateral movement in response to stimulation of a Salamander embryo. The neural mechanism involved is illustrated in Fig. 48. (Coghill: "Anatomy and the Problem of Behavior," cambridge Univ. Press.)
passively but ultimately acquire independence. Limb movements may thus be said to individuatefrdm the mass movement
oENEs1s oF FUNcTmN 1N NERvoUs sYsTEM 145


Fig. 51.—serial tracings from motion pictures of the early swimming stage of a
Salamander embryo. Resting position in 1 and to. (coghi11: «Anatomy and the
Problem of Behavior," cambridge Unim Press.)


Fig. Hex-Three diagrams to; show the development of the first and subsequent
waves of contraction which result in swimming in the Salamander embryo. (coghill: «Anatomy and the Problem of Behavior," cambridge Unim Press.)


of the trank. Terrestrial locomotion, the feeding reaction and
Later, as the 1imbs grow out they first move with the trunlc passively but ultimately acquire independence. Limb movements may thus be said to individuatefrdm the mass movement of the trank. Terrestrial locomotion, the feeding reaction and other activities are made possible by brealcing up of the original total pattern or by the formation of segondary patterns within it. 0ther more discrete reflexes individuate from these patterns as development proceeds. « An independent and integrated motor system is present in fishesfor some time before it is captured by developing sensory mechanisms. During this period of independence the motor system can respond to changes in the internal but not the external environment. 19
other activities are made possible by brealcing up of the original
total pattern or by the formation of segondary patterns within


10
146 Pnvssror.ocv oF THE FETUs


it. 0ther more discrete reflexes individuate from these patterns
as development proceeds. « An independent and integrated motor
system is present in fishesfor some time before it is captured by
developing sensory mechanisms. During this period of independence the motor system can respond to changes in the internal
but not the external environmenr.U


In 1929 Coghillsl lattempted to explain behavior in human
embryos studied by Minlcowslci32 and others in terms of the total
pattern of the Salamander. He concluded that behavior in man
follows a developmental plan of a similar type. Some of the
earlier systcespmatic studies on development of fetal movements in
other mammals2s 9 suggested very strongly that nearly all embryonic motility develops from mass reactions resembling total
patterns. The more recent interpretations of these observations
will be discussed in the latter part of the present chapter.


Human and other mammalian embryos are so very different
'''Fig. 51.''' Serial tracings from motion pictures of the early swimming stage of a Salamander embryo. Resting position in 1 and to. (Coghi11: "Anatomy and the Problem of Behavior," Cambridge Univ. Press.)
from Amblystoma at the time movements and reflexes first appear
that it is surptising to find any functional similarities. The larval
Salamander develops its total reaction and precisely integrated
side to side waves of movement within this integrated pattern
before limbs and mouth have been formed. Mammalian embryos
are far from having attained functional age at a comparable stage
in morphologic dilferentiation (compare Figs. 47 and Ho) .
Muscle is entirely l·aclcing. Within the embryonic central nervous
system of mammals no structures exist which are comparable
with the chains of transient afkerent Rohon-Beard cells of lower
forms. Furthermore, the motor neurons are arranged segmentally
rather than in longitudinal series and they do not appear to be
connected with one another. The ear1iest secondary neurons
of the spinal cord build tracts that are predominantly ascending
pathways. 1n the brain, the descending tracts send few übers into
the spinal cord until spinal behavioral responses have become
establishedkHs « In other word-s, there is no longitudinally integrating mechanism in the spinal cord of mammalian embryos at
the stage in development which corresponds to the early motile


« Recently Aug-Mo« has reported that the media1 longitudinal fascicle of the


spinal cord is the descending integrating tract for the mass reaction of the rat
'''Fig. 52.''' Three diagrams to; show the development of the first and subsequent waves of contraction which result in swimming in the Salamander embryo. (Coghill: "Anatomy and the Problem of Behavior," Cambridge Univ. Press.)
embryo and that its termination forms the ventral spinal commissure. This is at
variance with our own observations which show that the ventral commissure übers


arise in the spinal cord and ascend in the vgntraltuniculus
GENESIS OF FUNCTION IN NERVOUS sYsTEM 147


Amblystomaz nor is there until some time later. By the time
dikkerentiation of structure makes functional activities possible
the head and limbs have become prominent structures.


In the further course of development of mammalian embryos
these parts exert an ever increasing dominance over the trunk,
and growth in the nervous system responds to this dominance.
There is never a need for the type of aquatic locomotor total pattern which is found in the iishes and amphi«bians.


EARLY REFLEXES IN MÄMMALIAN BMBRYOS
In 1929 Coghillsl lattempted to explain behavior in human embryos studied by Minlcowski32 and others in terms of the total pattern of the Salamander. He concluded that behavior in man follows a developmental plan of a similar type. Some of the earlier systcespmatic studies on development of fetal movements in other mammals2s 9 suggested very strongly that nearly all embryonic motility develops from mass reactions resembling total patterns. The more recent interpretations of these observations will be discussed in the latter part of the present chapter.


True behavior makes its appearance about one ·««day after it
was Erst possible to elicit muscle contractions in embryos of the
rat, guinea pig, cat and sheep. It is essential to emp1oy experimental methods which do not impair the physiologic conditions of pregnant animals and their embryos to observe the tirst
reflexes. F urthermore, studies must be conducted immediately
upon opening the uterus because this operation invariably interferes with placental respiratory exchange, resulting in anoxemia.
The procedures used in such studies have been discussed in the
first chapter.


Although the description of early reflex responses which follows pertains primarily to cat embryos about 14 mm. crownrump lengthP similar results have been obtained in other mammals.3- «« C« «« When an embryo with placenta still attached to the
Human and other mammalian embryos are so very different from Amblystoma at the time movements and reflexes first appear that it is surptising to find any functional similarities. The larval Salamander develops its total reaction and precisely integrated side to side waves of movement within this integrated pattern before limbs and mouth have been formed. Mammalian embryos are far from having attained functional age at a comparable stage in morphologic dilferentiation (compare Figs. 47 and Ho) . Muscle is entirely l·aclcing. Within the embryonic central nervous system of mammals no structures exist which are comparable with the chains of transient afkerent Rohon-Beard cells of lower forms. Furthermore, the motor neurons are arranged segmentally rather than in longitudinal series and they do not appear to be connected with one another. The ear1iest secondary neurons of the spinal cord build tracts that are predominantly ascending pathways. 1n the brain, the descending tracts send few übers into the spinal cord until spinal behavioral responses have become established. 33-36 * In other words, there is no longitudinally integrating mechanism in the spinal cord of mammalian embryos at the stage in development which corresponds to the early motile Amblystoma; nor is there until some time later. By the time dikkerentiation of structure makes functional activities possible the head and limbs have become prominent structures.
uterine wall has been brought quickly into view and the intact
amniotic sac is percussed witli some blunt instrument, pressure
transmitted to the embryo through the amniotic fluid results in
quick outward and backward movement of the forelimb. The
movement may be called a twitch or jerk. similar responses are
obtainable in other ways. Flipping the limb gently with a needle
or a hair passed through the amnion serves equally well. In a
few instances it was even possible to elicit this reaction by lightly
touching certain points upon the forelimb. Furthermore, faradic
shocks applied to approximately the same points by means of
micro-electrodes gave rise to similar quick outward and backward
movements of the limb.


Another reaction is frequently elicitable in embryos 14 mm.
long. stimulation of the forward end of the head. especially the
snoutz results in extension of the head. When the stimulus is
148 PHYSIOLOGY or THE FETUs


applied to one side ok the midline the head moves toward the opposite side and baclcwardH When the tip ok the snout is stimu1ated
* Recently Angulo 37 has reported that the media1 longitudinal fascicle of the spinal cord is the descending integrating tract for the mass reaction of the rat embryo and that its termination forms the ventral spinal commissure. This is at variance with our own observations which show that the ventral commissure fibers arise in the spinal cord and ascend in the vgntral funiculus.
it moves baclcward. Because this head response is more resistant
to changing physiologic conditions than that of the korelimb it
usually persists a little longer. Under the best conditions it too
is a quiclc movementz It has been observed by all investigators,
although some have encountered it at an earlier stage than others.


The head and korelimb responses are entirely separate and
distinct from one another when they iirst appear. They difker
somewhat in respect to the types ok stimulation eliciting them but
both seem to require stronger stimuli at first than they do at a
slightly later stage in development. The head movements, being
contralateral and involving muscles some little distance away


from the site of stimulation, are certainly reflexes. All observers
agree on this point. However, some have doubted the reflex nature ok the korelimb reactions, holdingsthat they may be due to
stimulation ok the muscles directly. The evidence, which will be
reviewed brieilyy kavors the view that they too are simple spinaltype reHexes.


Although the limb muscles can be induced to contract by
direct stimulation in asphyxiated embryos, the response held to be
a reflex is (a) elicitable kor only a briek interval (okten only a
kew seconds) while« metabolic conditions ok the embryo are at
their best. states of anoxemia set up experimentally make it impossible to obtain the reactions. Akter adequate direct stimulation the new muscle tends to relax slowly, whereas the reHex-like
response (b) seems to be a quiclcer movement with more rapid relaxation. Embryonic muscle appears to respond instantaneously
to directly app1ied stimuli, but (c) there is an interval just per—
ceptible· between stimulus and response ok thexeiiex type. 0ne
muscle contraction after another can be induced by direct stimulation, but (d) a second reflezklilce reaction cannot be made to kollow the Erst one until a briek interval ok time, a rekractory or
katigue period, has elapsed. Finally, (e) the responses believed to
be reilexes are stereotyped and do not show the molding characterizing direct contractions when the position ok the stimulus is
varied.


0ther experimental evidence demonstrates that the korelimb
In the further course of development of mammalian embryos these parts exert an ever increasing dominance over the trunk, and growth in the nervous system responds to this dominance. There is never a need for the type of aquatic locomotor total pattern which is found in the iishes and amphi«bians.
movements are reflexes. When xtiicroelectrodes are used to stimGENEsIs OF FUNCTION IN NERVOUS sYsTEM 149


ulate an embryo over the spinal cord some distance caudal to the
==Early Reflexes in Mammalian Embryos==
forelimb, the same quiclc outward and baclcward twitch results.
This is due to conduction up the spinal cord; stimuIation of other
parts of the embryo, equally distant from the limbs, does not pro—
duce this movement. At least one synapse is involved as indicated in Fig. 53.


The conception of the refiex nature of the early forelimb response iinds further confirmation in histologic studies in the
True behavior makes its appearance about one day after it was Erst possible to elicit muscle contractions in embryos of the rat, guinea pig, cat and sheep. It is essential to emp1oy experimental methods which do not impair the physiologic conditions of pregnant animals and their embryos to observe the tirst reflexes. Furthermore, studies must be conducted immediately upon opening the uterus because this operation invariably interferes with placental respiratory exchange, resulting in anoxemia. The procedures used in such studies have been discussed in the [[Book - Physiology of the Fetus 1|first chapter]].
spinal cords and peripheral nerves of the very specimens which
showed the reaction and which were subsequently stained by the


Fig. zssdiagram illustrating the probable nervous elements involved in elicits
ing forelimb movement by faradic stimulation of the spinal cord of an early main
malian embryo.


Ranson pyridine-silver techniquekss THE All nervous elements
Although the description of early reflex responses which follows pertains primarily to cat embryos about 14 mm. crownrump lengthP similar results have been obtained in other mammals. 3,4,6,7 When an embryo with placenta still attached to the uterine wall has been brought quickly into view and the intact amniotic sac is percussed witli some blunt instrument, pressure transmitted to the embryo through the amniotic fluid results in quick outward and backward movement of the forelimb. The movement may be called a twitch or jerk. similar responses are obtainable in other ways. Flipping the limb gently with a needle or a hair passed through the amnion serves equally well. In a few instances it was even possible to elicit this reaction by lightly touching certain points upon the forelimb. Furthermore, faradic shocks applied to approximately the same points by means of micro-electrodes gave rise to similar quick outward and backward movements of the limb.
essential for reflex action are present in the embryonic spinal cord
but their intrinsic synaptic connections are incomplete at the
time muscles can be made to contract by stimulating them directly
and previous to the appearance of the reliexdilce responses. 0ne
iinds alferent neurons whose peripheral Ebers pass to the tissues
immediately beneath the' epithelium of the forelimb and whose
central branches constitute the dorsal roots and dorsal funiculus
of the spinal cord. The efkerent neurons are assembled in two
groups in the ventral gray matter of the spinal cord, a medial
150 PHYSIOLOGY OF THE« FETUS


nucleus for trunk innervation and a lateral nucleus for the arm.
The efferent axons courses into the muscles of the shoulder region
and end in simple terminations upon some of the muscle übers.
Commissural and associationa1 neurons are present in the dorsal
column. ,The former are numerous in the region just beneath the
dorsomedial border of the dorsa1 funiculus, while the latter tend
to accumulate nearer the ventrolateral border of this afferent
pathway. Commissural axons pursue a course ventrally through


J« « »F. - «. v · « ·s - fis, F; - »,«’-«»; J  l -,E"-Z««
Another reaction is frequently elicitable in embryos 14 mm. long. stimulation of the forward end of the head. especially the snoutz results in extension of the head. When the stimulus is applied to one side ok the midline the head moves toward the opposite side and baclcwardH When the tip ok the snout is stimu1ated it moves baclcward. Because this head response is more resistant to changing physiologic conditions than that of the korelimb it usually persists a little longer. Under the best conditions it too is a quiclc movementz It has been observed by all investigators, although some have encountered it at an earlier stage than others.


 


 
The head and forelimb responses are entirely separate and distinct from one another when they iirst appear. They difker somewhat in respect to the types of stimulation eliciting them but both seem to require stronger stimuli at first than they do at a slightly later stage in development. The head movements, being contralateral and involving muscles some little distance away from the site of stimulation, are certainly reflexes. All observers agree on this point. However, some have doubted the reflex nature ok the korelimb reactions, holdingsthat they may be due to stimulation ok the muscles directly. The evidence, which will be reviewed brieilyy kavors the view that they too are simple spinaltype reflexes.


-..-«. ·« JHJL J»
Fig. 54.-—Photo1nicrograph of the fifth cervical Segment of the spina1 cord of a
13 mm. cat embryo just before the time the Erst forelimb reflexes can be elicitedx
as» Ventral funiculus; tut» association neurons; c» cornmissurex ern» Commissural
neurons; ihn, dorsal root and ganglionx M» Iateral funiculusx m.l., motor nucleus
for the limb muscles; Max» motor nucleus for the trunlc musclesz p.f., dorsal funiculus. Compare with Fig. 56. Pyridinesjlver stainz X so.


- s « -. »«
Although the limb muscles can be induced to contract by direct stimulation in asphyxiated embryos, the response held to be a reflex is (a) elicitable kor only a briek interval (okten only a kew seconds) while« metabolic conditions ok the embryo are at their best. states of anoxemia set up experimentally make it impossible to obtain the reactions. Akter adequate direct stimulation the new muscle tends to relax slowly, whereas the reflex-like response (b) seems to be a quiclcer movement with more rapid relaxation. Embryonic muscle appears to respond instantaneously to directly app1ied stimuli, but (c) there is an interval just perceptible between stimulus and response ok thexeiiex type. 0ne muscle contraction after another can be induced by direct stimulation, but (d) a second reflezklilce reaction cannot be made to kollow the Erst one until a briek interval ok time, a rekractory or katigue period, has elapsed. Finally, (e) the responses believed to be reilexes are stereotyped and do not show the molding characterizing direct contractions when the position ok the stimulus is varied.
J» I ««


the gray matter and cross the kloor p1ate, to become an ascending
tract close to the motor nerve cells which supply the trank. Associational axons pass close to the motor nucleus for limb muscles
and enter the Iateral funicu1us. This relation of associational
neurons and primary motor forelimb neurons appears to be very
intimate, with axons of the former coursing parallel with dendrons
of the latter. However, up to the time of appearance of the forelimb response there is no close re1ationship between the primary
afferent and the secondary neurons (Fig. 54) . A few collatera1
CENESIS OF FUNCTION IN NERVOUS SYSTEM 151


branches of dorsal funiculus ftbers do pass for a very short distance
Other experimental evidence demonstrates that the korelimb movements are reflexes. When xtiicroelectrodes are used to stimulate an embryo over the spinal cord some distance caudal to the forelimb, the same quiclc outward and baclcward twitch results. This is due to conduction up the spinal cord; stimuIation of other parts of the embryo, equally distant from the limbs, does not produce this movement. At least one synapse is involved as indicated in Fig. 53.
toward the associational group, but not many have reached it.


In the early motile embryos in which reilezklike twitches of the
forelimb occurred when the limbs were flipped or when the
amniotic sac was percussed, connections have been comp1eted be—
tween the primary afkerent and the associati0na1 neurons. This is


.. 


« Z«
'''Fig. 53.''' Diagram illustrating the probable nervous elements involved in elicits ing forelimb movement by faradic stimulation of the spinal cord of an early mammalian embryo.


Fig. 55.-—Photoicrograph of the dorsal funiculus (zt).j.) f the spinal cord of:
a 13 mm. cat embryo showing the Erst collateral branches (col.) of primary aikerent
neuronsz these serve to complete the first spinal reflex arcs. Pyridinesilver stainx


X Hin.
The conception of the refiex nature of the early forelimb response iinds further confirmation in histologic studies in the spinal cords and peripheral nerves of the very specimens which showed the reaction and which were subsequently stained by the  Ranson pyridine-silver techniquekss THE All nervous elements essential for reflex action are present in the embryonic spinal cord but their intrinsic synaptic connections are incomplete at the time muscles can be made to contract by stimulating them directly and previous to the appearance of the reliexdilce responses. 0ne iinds alferent neurons whose peripheral Ebers pass to the tissues immediately beneath the' epithelium of the forelimb and whose central branches constitute the dorsal roots and dorsal funiculus of the spinal cord. The efkerent neurons are assembled in two groups in the ventral gray matter of the spinal cord, a medial nucleus for trunk innervation and a lateral nucleus for the arm. The efferent axons courses into the muscles of the shoulder region and end in simple terminations upon some of the muscle übers. Commissural and associationa1 neurons are present in the dorsal column. ,The former are numerous in the region just beneath the dorsomedial border of the dorsa1 funiculus, while the latter tend to accumulate nearer the ventrolateral border of this afferent pathway. Commissural axons pursue a course ventrally through the gray matter and cross the kloor p1ate, to become an ascending tract close to the motor nerve cells which supply the trank. Associational axons pass close to the motor nucleus for limb muscles and enter the Iateral funicu1us. This relation of associational neurons and primary motor forelimb neurons appears to be very intimate, with axons of the former coursing parallel with dendrons of the latter. However, up to the time of appearance of the forelimb response there is no close re1ationship between the primary afferent and the secondary neurons (Fig. 54) . A few collatera1 branches of dorsal funiculus fibers do pass for a very short distance toward the associational group, but not many have reached it.


accomplished when collateral branches grow in among the cells
of the dorsal gray horn from the sensory Hbers nearest the lateral
border of the dorsal funiculus Some of the longest collaterals
enter the nucleus of motor cells supplying the forelimb musc1es.
These relationships will be seen in accompanying photomicros
graphs (Figs. 54 and 55) and diagrams (Figs. 56 and 57) . The
organization of the first structural reflex mechanism is clearly such
152 PHYSIOLOGY OF THE FETUS


that when it begins to kunction the response will not only be
homolateraI but will be conlined to the segments at which the
impulses enter the spinal cordx The greatest number and the


Fig. 56.-camera lucida tracings ok the dorsal roots (d.s·.) and dorsal kuniculus
(d.f.) ok sheep embryos M) Do mai» (B) 23 kam» and (c) 24 nun. long. The
developrnent ok collaterals (col.) ok the dorsal kuniculus which curve rnedially
around the gelatinous substance (gel.) ok the gras matter is correlated with the
appearance ok the tirst korelitnb retiexes. Pyridinesilver stainz X 72.


Fig. 57.—Diagrammatic cross Section through the embryonic spinal cord just
'''Fig. 54.''' Photo1nicrograph of the fifth cervical Segment of the spina1 cord of a 13 mm. cat embryo just before the time the Erst forelimb reflexes can be elicitedx as» Ventral funiculus; tut» association neurons; c» cornmissurex ern» Commissural neurons; ihn, dorsal root and ganglionx M» Iateral funiculusx m.l., motor nucleus for the limb muscles; Max» motor nucleus for the trunlc musclesz p.f., dorsal funiculus. Compare with Fig. 56. Pyridinesjlver stainz x 80.
before (lekt side) and just after (right side) the completion ok reilex arcs malte
the earliest retiexes e1icitable. The earliest connections ok aiketent neurons (·a)
appear at the lateral end ok the dorsal kuniculus and complete unisegtnental reklex
arm. some ok these involve an interneuron but others (c) make direct connections
with the pritnary motor neurons kor the limb rnuscles. Only later do the dorsal
kuniculus übers krom lower segtnents ok the spinal c0rd connect with the Commissural interneurons by means ok collaterals O) and thus etkect contralateral trunk


tnovements.


longest new collateraIs lirst grow into the gray matter in the
In the early motile embryos in which reilezklike twitches of the forelimb occurred when the limbs were flipped or when the amniotic sac was percussed, connections have been comp1eted be— tween the primary afkerent and the associational neurons. This accomplished when collateral branches grow in among the cells of the dorsal gray horn from the sensory Hbers nearest the lateral border of the dorsal funiculus Some of the longest collaterals enter the nucleus of motor cells supplying the forelimb musc1es. These relationships will be seen in accompanying photomicros graphs (Figs. 54 and 55) and diagrams (Figs. 56 and 57) . The organization of the first structural reflex mechanism is clearly such that when it begins to kunction the response will not only be homolateraI but will be conlined to the segments at which the impulses enter the spinal cordx The greatest number and the longest new collaterals first grow into the gray matter in the brachial region and, correlatively, one linds the first reflex response involving the forelimbs.
brachial region and, correlatively, one linds the first reklex re—


sponse involving the korelimbs.
osksinsrs ori- FUNcUoN 1N NERvoUs sYsTEM 153


The correlation between completion of anatomical reflex
arcs in the spinal cords of cat embryos and the manifestation of
forelimb reiiex function has been confirmed in the chiclc, rat and
sheep. The stage of development reached in the spinal cord of
these four species at the time reiiexes appear varies to some extent,
but the responses occur in all at the time reflex arcs are ready
irrespective of other structural variations.


such evidence as has been disclosed by the correlated histologic and physiologic experiments reviewed here briefly leads to
'''Fig. 55.''' Photoicrograph of the dorsal funiculus (zt).j.) f the spinal cord of: a 13 mm. cat embryo showing the Erst collateral branches (col.) of primary aikerent neuronsz these serve to complete the first spinal reflex arcs. Pyridine-silver stain x 510.
the conclusion that the early foreIimb movements are local, uni—
segmentah homolateral two- and three—neuron reflexes. Mammalian behavior has its genesis, not in a mass reaction or total
pattern like that of lower vertebrates, but in these relatively Simple reilexes which are at first entirely nonintegrated.


OTHER SIUPLE REFLEXES AND TBZEIR MTEGRAT10N


During the course of development of cat embryos, many re—
flexes malte their appearance. Just as the first responses at the
shoulder can be elicited before the limbs move spontaneously and
before they move with the neclc and trank, local reilexes appear
at the elbow and wrist joints as separate entities before the distal
portions of the« limbs become integrated with other parts of the
body. Local liexion at the elbows occurs at about the 16—mm.
steige. It is often followed by other more distant movements,
such as bending at the shoulder or extension of the head and
Iiexion of the trank. However, these more proximal and cephalic
movements are not followed by rnovement at the elbow at this
time. similarly, local wrist movements seen in embryos about
17 mm. long, are at lirst unrelated to other movements.


Local movements at the proximal hind-leg joint, unintegrated
'''Fig. 56.''' Camera lucida tracings ok the dorsal roots (d.s·.) and dorsal kuniculus (d.f.) ok sheep embryos M) Do mai» (B) 23 kam» and (c) 24 nun. long. The developrnent ok collaterals (col.) ok the dorsal kuniculus which curve rnedially around the gelatinous substance (gel.) ok the gras matter is correlated with the appearance ok the tirst korelitnb retiexes. Pyridine-silver stainz X 72.
with trunlc responses, are encountered in specimens between 15
and 16 mm. long. Those at the lcnee appear at 17.5 mm. The
earliest independent motility of the tail is found at the same
steige.


Although the first head reilexes can be elicited by stimulating
only a small area near the tip of the snout in embryos 13—14 mm.
long, it is but a short time later that they occur in response to
stimulation of most of the facial area. In specimens 15—16 mm.
long, contralateral head flexion is obtainable from all parts of the
154 PHYSIOLOGY OF THE« FETUS


face except that supplied by the ophthalmic division of the trigem—
'''Fig. 57.''' Diagrammatic cross Section through the embryonic spinal cord just before (lekt side) and just after (right side) the completion ok reilex arcs malte the earliest retiexes e1icitable. The earliest connections ok aiketent neurons (·a) appear at the lateral end ok the dorsal kuniculus and complete unisegtnental reklex arm. some ok these involve an interneuron but others (c) make direct connections with the pritnary motor neurons kor the limb rnuscles. Only later do the dorsal kuniculus übers krom lower segtnents ok the spinal cord connect with the Commissural interneurons by means ok collaterals O) and thus etkect contralateral trunk movements.
inal nerve. From the ophthalrnic region, extension with flexion
to the same side occurs. With further developmenh stimulation
of more and more Portions of the face leads to the homolateral
response until, at about the 20 mm. stage, only the ear gives a contralateral head flexionk


These and other interesting reflex sactivities have been ob—
served in embryos. All possess an element of individuality at
first, but ultimately most of the local responses are brought together into more generalized movements. This comes about by
integration within the frameworlc of a growing central nervous
mechanism. Longitudinal tracts of nerve ftbers develop within
the spinal cord, and as they make connections with afkerent and
efkerent neurons they begin to exert an integrating function over
the local, isolated reactions.»


The earliest secondary pathway in the spinal cord is a ventral
longitudinal bundle, primarily an ascending tract formed by the
axons of commissural neurons. Impulses carried by it apparently
are able to discharge motor neurons supplying trunlc and neck
musc1es at more rostral 1evels. Cel1 bodies of the commissural
neurons, lying near the medial border of the dorsal funiculus,
receive impulses from primary afferent neurons which have been
coursing rostrally for some distance in the dorsal funiculus. Consequently the local homo1ateral forelimb reflex is sometimes followed, at the 15 to 1 6 mm. stage, by a contraction of neclc muscles
similarly at a later period, hind-limb reflexes are followed progressively by responses of the forelimbs and the neck. A progressive discharge of neurons from caudal to rostral regions of the
spinal cord is broughtlabout through integration of ascending
neurons of the primary afferent dorsal funiculus with the commissural secondary tract.


Nerve Ebers grow caudally into the spinal cord from centers
in the medulla oblongata and midbrain. Many of these occupy


»positions in the ventral funiculus but they do n’ot reach any given
The correlation between completion of anatomical reflex arcs in the spinal cords of cat embryos and the manifestation of forelimb reiiex function has been confirmed in the chiclc, rat and sheep. The stage of development reached in the spinal cord of these four species at the time reiiexes appear varies to some extent, but the responses occur in all at the time reflex arcs are ready irrespective of other structural variations.


point in the spinal cord until after ascending Ebers from a lower
spinal segment have reached the medulla oblongata. consequently stimulation of structures near the caudal end of an
embryo of about 18 mm. (Fig. 58) can result sequentially in (a)
local reflexes, (b) reflexes of more rostral .parts, (c) head moves


GENESIS OF FUNCTION IN NERVOUS sYsTEM 155
such evidence as has been disclosed by the correlated histologic and physiologic experiments reviewed here briefly leads to the conclusion that the early foreIimb movements are local, uni— segmentah homolateral two- and three—neuron reflexes. Mammalian behavior has its genesis, not in a mass reaction or total pattern like that of lower vertebrates, but in these relatively Simple reilexes which are at first entirely nonintegrated.


ments and then (d) the trunk activities which are integrated with
==Other Siuple Reflexes and Their Integration==
the head and which always fall just short of the most recently
acquired local responses. The descending integrating tracts of
nerve ftbers are so placed in the ventral portion of the spinal
cord that when activated they can more eifectively bring about
discharge of motor cells which supp1y the trunk muscles than
neurons for the limb muscles. As a result of such an arrangement
the limhs seem not to be completely integrated with the trunk
during the early embryonic period. Later the association be—
comes more intimate. 0n the other hand, the trunlc movements
become integrated with those of the neclc almost as soon as they


Fig. 58.-—Cat embryo 18.5 mm. C. R. 1ength, from which local reHexes as well
During the course of development of cat embryos, many re— flexes malte their appearance. Just as the first responses at the shoulder can be elicited before the limbs move spontaneously and before they move with the neclc and trank, local reilexes appear at the elbow and wrist joints as separate entities before the distal portions of the« limbs become integrated with other parts of the body. Local flexion at the elbows occurs at about the 16—mm. steige. It is often followed by other more distant movements, such as bending at the shoulder or extension of the head and flexion of the trunk. However, these more proximal and cephalic movements are not followed by rnovement at the elbow at this time. similarly, local wrist movements seen in embryos about 17 mm. long, are at first unrelated to other movements.
as early integrated movements could be elicited. Magniiication is the same as that


in Figs. 44 and 47.


begin to appear at the 15 mm. stage. With growth in size of the
Local movements at the proximal hind-leg joint, unintegrated with trunlc responses, are encountered in specimens between 15 and 16 mm. long. Those at the lcnee appear at 17.5 mm. The earliest independent motility of the tail is found at the same stage.
individual, more and more muscles of the back are added to the
trunk activities in a caudal1y expanding Progression.


Some recent experiments involving the production of states of
anoxemiaU have added important information to our conception
of the relation of simple reHexes to the more massive integrated
activities of cat embryos. When decerebrate cats were allowed to
breathe atmospheres low in oxygen before the uterus was opened
it was found that local reflexes became depressetd and the integrated head and trunk movements were exaggerated and more
sustained or tonic than normally. Irritability of the embryos wszas
is6 isiiYsiohocY or THE Fixsrus


diminished during anoxemia. Extended use ok the gas mixture
Although the first head reilexes can be elicited by stimulating only a small area near the tip of the snout in embryos 13—14 mm. long, it is but a short time later that they occur in response to stimulation of most of the facial area. In specimens 15—16 mm. long, contralateral head flexion is obtainable from all parts of the face except that supplied by the ophthalmic division of the trigem— inal nerve. From the ophthalrnic region, extension with flexion to the same side occurs. With further developmenh stimulation of more and more Portions of the face leads to the homolateral response until, at about the 20 mm. stage, only the ear gives a contralateral head flexion.
brought about more complete anoxemia and all responses ceased.
spontaneous movements and responses to stimulation ok embryos
studied under conditions ok partial anoxemia resemble mass reactions and might easily lead one to the conclusion that behavior
develops in mammalss in a manner very similar to that in the
Salamander. Only when such conditions are avoided can the


various simple reflexes be observed as separate elements.


REFERENCES CITED
These and other interesting reflex sactivities have been ob— served in embryos. All possess an element of individuality at first, but ultimately most of the local responses are brought together into more generalized movements. This comes about by integration within the frameworlc of a growing central nervous mechanism. Longitudinal tracts of nerve ftbers develop within the spinal cord, and as they make connections with afkerent and efkerent neurons they begin to exert an integrating function over the local, isolated reactions.
 
 
The earliest secondary pathway in the spinal cord is a ventral longitudinal bundle, primarily an ascending tract formed by the axons of commissural neurons. Impulses carried by it apparently are able to discharge motor neurons supplying trunk and neck musc1es at more rostral 1evels. Cel1 bodies of the commissural neurons, lying near the medial border of the dorsal funiculus, receive impulses from primary afferent neurons which have been coursing rostrally for some distance in the dorsal funiculus. Consequently the local homo1ateral forelimb reflex is sometimes followed, at the 15 to 1 6 mm. stage, by a contraction of neclc muscles similarly at a later period, hind-limb reflexes are followed progressively by responses of the forelimbs and the neck. A progressive discharge of neurons from caudal to rostral regions of the spinal cord is broughtlabout through integration of ascending neurons of the primary afferent dorsal funiculus with the commissural secondary tract.
 
 
Nerve fibers grow caudally into the spinal cord from centers in the medulla oblongata and midbrain. Many of these occupy positions in the ventral funiculus but they do n’ot reach any given point in the spinal cord until after ascending Ebers from a lower spinal segment have reached the medulla oblongata. consequently stimulation of structures near the caudal end of an embryo of about 18 mm. (Fig. 58) can result sequentially in (a) local reflexes, (b) reflexes of more rostral .parts, (c) head movements and then (d) the trunk activities which are integrated with the head and which always fall just short of the most recently acquired local responses. The descending integrating tracts of nerve ftbers are so placed in the ventral portion of the spinal cord that when activated they can more eifectively bring about discharge of motor cells which supp1y the trunk muscles than neurons for the limb muscles. As a result of such an arrangement the limhs seem not to be completely integrated with the trunk during the early embryonic period. Later the association becomes more intimate. 0n the other hand, the trunlc movements become integrated with those of the neclc almost as soon as they begin to appear at the 15 mm. stage. With growth in size of the individual, more and more muscles of the back are added to the trunk activities in a caudal1y expanding Progression.
 
 
 
'''Fig. 58.''' Cat embryo 18.5 mm. C. R. 1ength, from which local reHexes as well as early integrated movements could be elicited. Magniiication is the same as that in Figs. 44 and 47.
 
 
 
 
Some recent experiments involving the production of states of anoxemiaU have added important information to our conception of the relation of simple reHexes to the more massive integrated activities of cat embryos. When decerebrate cats were allowed to breathe atmospheres low in oxygen before the uterus was opened it was found that local reflexes became depressetd and the integrated head and trunk movements were exaggerated and more sustained or tonic than normally. Irritability of the embryos wss diminished during anoxemia. Extended use ok the gas mixture brought about more complete anoxemia and all responses ceased. spontaneous movements and responses to stimulation ok embryos studied under conditions ok partial anoxemia resemble mass reactions and might easily lead one to the conclusion that behavior develops in mammalss in a manner very similar to that in the Salamander. Only when such conditions are avoided can the various simple reflexes be observed as separate elements.
 
==References Cited==


i. swenson, E. A. i9e6. Thesis, Univ. Kansas.
i. swenson, E. A. i9e6. Thesis, Univ. Kansas.


e. Angulo y Gonzalez A. W. i93e. comp. Neur., ss: 39s.
e. Angulo y Gonzalez A. W. i93e. comp. Neur., ss: 39s.


z. Raney, E. T. sc L. carmichaeL i934. Genetic Psychol., 4s: Z.
z. Raney, E. T. sc L. carmichaeL i934. Genetic Psychol., 4s: Z.


4. Windle, W. F., W. L. Minear, M. F. Austin sc D. W. 0rr. i93s. Physiol.
4. Windle, W. F., W. L. Minear, M. F. Austin sc D. W. 0rr. i93s. Physiol.
Line 598: Line 191:
s. carmichaels L. i934. Genetic Psychol. Mono., is: 337.
s. carmichaels L. i934. Genetic Psychol. Mono., is: 337.


6. Bridgmaix c. s. sc L. cariiiichaeL i93s. J. Genetic Psychol., 47: e47.
6. Bridgmaix c. s. sc L. cariiiichaeL i93s. J. Genetic Psychol., 47: e47. 7. Barcrokh J» D. H. Bari-on sc W. F. Windle. i936. J. Physiol» s7: 73. s. Barcroktz sc D. I-I. Barron. i939. comp. Neur., 7o: 477.
7. Barcrokh J» D. H. Bari-on sc W. F. Windle. i936. J. Physiol» s7: 73.
s. Barcroktz sc D. I-I. Barron. i939. comp. Neur., 7o: 477.


9
9 o
o


. Windle, W. F. sc A. M. Griklin. i93i. J. comp. Neur., se: i49.
. Windle, W. F. sc A. M. Griklin. i93i. J. comp. Neur., se: i49. . Windle, W. F., J. E. 0’Donnell sc E. E. Glasshagle i933. Physiol. Zool.,
. Windle, W. F., J. E. 0’Donnell sc E. E. Glasshagle i933. Physiol. Zool.,


6- sei.
6- sei.


ii. Windle, W. F., D. W. 0rr sc W. L. Minear. i934. Physiol. Zool» 7: 6oo.
ii. Windle, W. F., D. W. 0rr sc W. L. Minear. i934. Physiol. Zool» 7: 6oo. ie. Windle, W. F. sc R. F. Becken i94o. Arch. Neun Psychiat., 43: ge.
ie. Windle, W. F. sc R. F. Becken i94o. Arch. Neun Psychiat., 43: ge.


i Z. coronios, J. D. i933. Genetic Psychol. Mono., i4: es3.
i Z. coronios, J. D. i933. Genetic Psychol. Mono., i4: es3.
Line 621: Line 209:
is. I-Iooker, D. i936. Yale J. Biol. Med., s: s79.
is. I-Iooker, D. i936. Yale J. Biol. Med., s: s79.


i6. Preyeix W. isss. specielle Physiologie des Embryo. Stichen, Leipzig.
i6. Preyeix W. isss. specielle Physiologie des Embryo. Stichen, Leipzig. i7. Pankratz D. s. i93i. Anat. Rec., 49: 3i.
i7. Pankratz D. s. i93i. Anat. Rec., 49: 3i.
 
is. coghilh G. E. i9e9. Anatomy and the Problem ok Behavioic Macmib


lau, New York.
is. coghilh G. E. i9e9. Anatomy and the Problem ok Behavioic Macmillan, New York.


i9. Tracy, I-I. C. i9e6. J. comp. Neur., 4o: es3.
i9. Tracy, I-I. C. i9e6. J. comp. Neur., 4o: es3.
Line 644: Line 229:
es. Windle, W. F. i939. Physiol. Zool» ie: 39.
es. Windle, W. F. i939. Physiol. Zool» ie: 39.


e7. Angulo y Gonealez A. W. i933. Proc. soc. Exp. Biol. sc Med., zi- ii»i.
e7. Angulo y Gonealez A. W. i933. Proc. soc. Exp. Biol. sc Med., zi- ii»i. es. Windle, W. F. i937. 1bid., Zö- 64o.
es. Windle, W. F. i937. 1bid., Zö- 64o.


e9. scharpenberg, L. G. sc W. F. Windle. ig3s. Anat» 7e: 344.
e9. scharpenberg, L. G. sc W. F. Windle. ig3s. Anat» 7e: 344.


so. carmichaeL L. i933. 1n C. Murchison’s I-Iandb. child Psychol» end ed»
so. carmichaeL L. i933. 1n C. Murchison’s I-Iandb. child Psychol» end ed»
Line 653: Line 237:
chap. e, P. 3i, clarlc Univ. Press, Worcestetx Mass
chap. e, P. 3i, clarlc Univ. Press, Worcestetx Mass


3i. coghilh G. E. i9e9. Arch. Neun sc Psychiat., ei: 989.
3i. coghilh G. E. i9e9. Arch. Neun sc Psychiat., ei: 989. GENEsIs OF FUNCTION IN NERVOUS sYsTEM 157
GENEsIs OF FUNCTION IN NERVOUS sYsTEM 157


ge. Minlcowslch M. 1922. Schweiz. mecL Woche-weht» He: 721, 751.
ge. Minlcowslch M. 1922. Schweiz. mecL Woche-weht» He: 721, 751. 33. Windle, W. F. 1934. J. comp. Neun, 59: 487.
33. Windle, W. F. 1934. J. comp. Neun, 59: 487.


34. Windle, W. F. 8c D. W. Ort. i934. Ibid., so: 287.
34. Windle, W. F. 8c D. W. Ort. i934. Ibid., so: 287.
Line 666: Line 248:


37. Angulo y Gonzalez A. W. 1939. Ibic1., 71: 325.
37. Angulo y Gonzalez A. W. 1939. Ibic1., 71: 325.
{{Footer}}

Revision as of 10:44, 10 September 2018

Embryology - 24 Apr 2024    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Windle WF. Physiology of the Fetus. (1940) Saunders, Philadelphia.

1940 Physiology of the Fetus: 1 Introduction | 2 Heart | 3 Circulation | 4 Blood | 5 Respiration | 6 Respiratory Movements | 7 Digestive | 8 Renal - Skin | 9 Muscles | 10 Neural Genesis | 11 Neural Activity | 12 Motor Reactions and Reflexes | 13 Senses | 14 Endocrine | 15 Nutrition and Metabolism | Figures

Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Chapter X The Genesis of Function in the Nervous System

THE beginning of functional activity in the nervous system has been investigated most thoroughly in embryos of the rat,I-4 guinea pig,5- S sheepfs 8 and cat,9-13 and less completely in man14s 15 and other mammals.10-I7 studies in the lower vertebrates,18-22 especially amphibia, have influenced conceptions of behavioral de— velopment in mammals to a very considerable extent. A complete review of all articles on the subject of early fetal movements would require far more space than is available in the present chapter.



Fig. 47. Embryos of the (A) rat, (B) cat and (C) human at approximately the stage in development at which simple rellexes are expected for the first time. crownckump length: 12 mm. rat; 14 mm. cat; 18 mm. human (7 weeks). Magnificatiom X Z.


1t is impossible to say precisely when nerve cells attain the ability to discharge or when kibers can conduct nervous impulses for the first time. However, muscle contractions induced by nervous activity can be elicited surprisingly early in prenatal life. The stage at which nervous function is first observable in mammals varies to some extent, but in all species that have been investigated it is before body form has talcen on the characteristic appearance of the species. In other words, somatic movements start before the close of the embryonic, rather than in the fetal period. This is illustrated by the accompanying photographs of rat, cat and human embryos talcen at about the time simple reHexes can first be induced (Fig. 47) .


The initiation of function in slceletal muscle cells was considered in the preceding chapten Myogenic xesponses precede reiiexes by at least one day in most mamma1s. The development of muscle iibers and of motor nerves with simple epilemmal motor nerve endings goes hand -in hand, but there does not seem to be an immediate correlation between the appearance of motor end— ings and Csunctional reflexes as some have suggestedks From the structural point of view it is possible that muscle contractions can be induced by discharge of motor neurons before reflex arcs have been completely formed. With the advent of conduction from afferent to efkerent neurons through synaptic centers, reHex re— sponses to stimulation are manifested. At this point in deve1opment behavior may be said to have its genesis.

Myogenic Responses

Let us examine the antecedents of behavioral genesis in somewhat gyeater detail. spontaneous muscle twitching characterizes embryos of certain lower vertebrates before reHex excitation becomes eifective. 0bservations in fishes are especially notable.I9 The similarity to spontaneous contractions of myob1asts and muscle iibers in cultures of embryonic chiclc tissues is striking. It is possible that some of the earliest spontaneous movements »observed in the intact living chick embryo1S-21-24-25 are of this nature.


No comparable phenomenon has been seen in .mammalian embryos studied under normal physiologic conditions. However, the movements which manifest themselves in ionically unbalanced saline solutions probably are myogenic responsesKs Why spontaneous muscle twitching is not encountered normally in mammalian embryos has not been determined. Musculature is laid down well in advance of the time it can be activated reflexly in the rat, guinea pig, sheep and cat.


Mechanical and electrical stimuli applied directly to muscle masses of intact embryoX efkect contractions readily. Microselecs trodes constructed of Hne nichrome wires insulated except at the tips serve admirably for deliveringdocalized faradic shoclcs. Contractions of the embryonic slceletal muscles induced in this manner possess certain characteristics which distinguish them from other types of somatic movement. They are as follows: (a) a minimal stimulus, just adequate to produce a response, gives rise to a quiclc contraction followed by a slower relaxationx (b) each succeeding stimulation produces a similar contraction, for there is no noticeable interval of fatigue during which the muscle is re— fractoryz (c) the contraction is remarlcably well localized in a small region immediately around the tips of the electrodes and consequently -movements in several planes can usually be brought about by shifting the Position of the electrodes; (d) the embryonic muscle tissue retains a high degree of excitability irrespective of great changes in metabolic conditions. In fact, specimens which have been allowed to bleed until white, which have cooled to room temperature and in which the heart has practically stopped beating still respond to direct stimulation of the slceletal musculature.


All the muscles of an embryo do not simultaneously reach a state of development in which contractions are possible. The first in which such direct responses can be observed are those ok the forelimbs at the attachment to the body. With advancement of growth,.excitability spreads both rostrally and caudally as well as distally from these points.

Neuromotor Responses

The second step in development of behavior is thought to be the appearance of muscle contraction in response to. excitation of motor neurons.27 Nerve endings of a primitive lcind (Fig. 45) are present upon developing muscle übers at a time when the only somatic movements are those which follow direct skimulation of the muscleskss 29 Although it has been impossible to obtain direct evidence in the youngest cat embryos that purely neuromuscular contractions precede rellexes, such contractions can be demonstrated in specimens a little more advanced, in which reflex responses are already obtainable. After the reflexes have died away with deterioration of the· physiologic oonditions of the embryo, stimulation of motor centers produces movements. A s1ender and sharp dental broach was used to pierce the tissues of the back and the spinal cord of the embryos. It was found that a backward movement of the forelimb followed when the instrument was passed into the spinal cord at the level between C.7 and T.1 and a forward movement resulted in the same specimens when it was inserted at the level between c.4 and c.6. The true reflexes which had been obtained previously were all baclcward and outward movements of the 1imbs. Thus it is apparent that a new forward movement of the arm had been induced by direct stimulation of a motor center before such a movement occurred as the result of retlex stimulation of afferent nerves. It is especially noteworthy that the responses were localized and that there was no diffuse spreading of excitation through the center even with this rather crude form of stimulation. The segmentaL nonintegrated character of the motor ce11 column of the embryonic spinal cord, so clearly evident in silver-stained histologic preparations, is demonstrable by physiologic methods.


Genesis Of Reflex Behavior

The third step in behavioral development is characterized by the appearance of reflexes. These do not manifest themselves unti1 atkerent and efferent neurons, simple nerve endings in peripheral tissues, connector neurons in the central nervous system and functional synaptic central mechanisms have been formed.


There are essentially two conceptions of the development of behavior in mammalian embryos. 0ne group of investigatorsY II· IS believe that they have demonstrated the genesis of reflexes by a process of individuation from a fully integrated mass reaction or «total Patter·n." In other words, they believe that more or less discrete movements are not the primary units of behavior but that local reflexes difkerentiate from a more fundamental baclcground of massive movement. Another group of investigatorsws 30 hold the opposjng view that the basic elements in the genesis of mammalian behavior are relatively simple reliex re— sponses. They lind that the more complex reactions of older fetuses are formed by progressive neuronal integration of the less complicated activities of the embryo. some other investigators 2 maintain that both theories are partially true, but are inclined to kavor the former.

The Concept of a Total Pattern

The doctrine of development of behavior from a total pattern is based on a long series of correlated physiologic and histologic studies by coghill in the urode1e amphibiam Amblystoma, ap— pearing frequently since 1913 and summarized in his London lectures. 18 It was found that a motor mechanism develops on either side of the embryonic floor plate as a longitudinally conducting system of neurons. Each neuron extends a process caudally to the next one; from this Process branches run to the muscles of the baclc and later to the 1imbs. Thesseries of neurons constitutes an integrating motor system which is laid down before kunction appears. An integrating s«ensory system is kormed by temporary neurons, the Rohon-Beard ce11s in the dorsal portion ok the spinal cord. They too send out processes, but in a rostral direction, with branches running to the epithelium and the muscles. The motor and sensory systems become connected by commissural fioorplate neurons, appearing iirst near the rostral end ok the embryo. These relations are illustrated in Figs. 48 and 49.



Fig. 48. Diagram of the sensoryimotor mechanism of the Salamander embryo which acoounts for the cephalwcaudal progkession of movement away from the side stimulated Arrows indicate direction of conductiom (Coghi11: "Anatomy and the Problem of Behavior," Cambridge Univ. Press.)


Fig. 49. Diagram of the neuromotor mechanism ok the Salamander embryo which allows an initial irnpulse (a, w) to be kollowed by a oontralatetal secondary Impulse (c, X) through an intermediate connecting neuron (b) . This makes pos— sible the swimming rnovernents like those in Fig. He. (coghi11: «Anatomy and the Problem ok Behavior," cambridge Univ. Press.)


A stimulus which is applied to one side of the embryonic salamander sets up impulses which are conducted rostra11y in the sensory System, across the· kloopplate neurons near its rostral end, and then caudally in the integrating motor System. contralateral flexion is thereupon the iirst true» behavioral responsez it is a mass movement or fully integrated response ’from the very start. This reaction is iliustrated in a series of drawings taken from a motion-picture record« (Fig. Ho) . The single flexion stage is followed shortly by bilateral ilexion and then by typical swimming. The latter depends upon the appearance of collateral branches of motor neurons (Fig. 49) which allow the caudal1y flowing impulses of one side ·to precede those of the other. In this way two waves of movement can course down the trunlc as shown in Figs. 51 and 52. 0ne response coming upon another in this manner produces forward propulsion of the embryo, establishing aquatic locomotion.



Fig. 50. Serial tracings from motion pictures (frame numhers indicatety of the earliest contralateral movement in response to stimulation of a Salamander embryo. The neural mechanism involved is illustrated in Fig. 48. (Coghill: "Anatomy and the Problem of Behavior," cambridge Univ. Press.)


Later, as the 1imbs grow out they first move with the trunlc passively but ultimately acquire independence. Limb movements may thus be said to individuatefrdm the mass movement of the trank. Terrestrial locomotion, the feeding reaction and other activities are made possible by brealcing up of the original total pattern or by the formation of segondary patterns within it. 0ther more discrete reflexes individuate from these patterns as development proceeds. « An independent and integrated motor system is present in fishesfor some time before it is captured by developing sensory mechanisms. During this period of independence the motor system can respond to changes in the internal but not the external environment. 19



Fig. 51. Serial tracings from motion pictures of the early swimming stage of a Salamander embryo. Resting position in 1 and to. (Coghi11: "Anatomy and the Problem of Behavior," Cambridge Univ. Press.)


Fig. 52. Three diagrams to; show the development of the first and subsequent waves of contraction which result in swimming in the Salamander embryo. (Coghill: "Anatomy and the Problem of Behavior," Cambridge Univ. Press.)



In 1929 Coghillsl lattempted to explain behavior in human embryos studied by Minlcowski32 and others in terms of the total pattern of the Salamander. He concluded that behavior in man follows a developmental plan of a similar type. Some of the earlier systcespmatic studies on development of fetal movements in other mammals2s 9 suggested very strongly that nearly all embryonic motility develops from mass reactions resembling total patterns. The more recent interpretations of these observations will be discussed in the latter part of the present chapter.


Human and other mammalian embryos are so very different from Amblystoma at the time movements and reflexes first appear that it is surptising to find any functional similarities. The larval Salamander develops its total reaction and precisely integrated side to side waves of movement within this integrated pattern before limbs and mouth have been formed. Mammalian embryos are far from having attained functional age at a comparable stage in morphologic dilferentiation (compare Figs. 47 and Ho) . Muscle is entirely l·aclcing. Within the embryonic central nervous system of mammals no structures exist which are comparable with the chains of transient afkerent Rohon-Beard cells of lower forms. Furthermore, the motor neurons are arranged segmentally rather than in longitudinal series and they do not appear to be connected with one another. The ear1iest secondary neurons of the spinal cord build tracts that are predominantly ascending pathways. 1n the brain, the descending tracts send few übers into the spinal cord until spinal behavioral responses have become established. 33-36 * In other words, there is no longitudinally integrating mechanism in the spinal cord of mammalian embryos at the stage in development which corresponds to the early motile Amblystoma; nor is there until some time later. By the time dikkerentiation of structure makes functional activities possible the head and limbs have become prominent structures.


  • Recently Angulo 37 has reported that the media1 longitudinal fascicle of the spinal cord is the descending integrating tract for the mass reaction of the rat embryo and that its termination forms the ventral spinal commissure. This is at variance with our own observations which show that the ventral commissure fibers arise in the spinal cord and ascend in the vgntral funiculus.



In the further course of development of mammalian embryos these parts exert an ever increasing dominance over the trunk, and growth in the nervous system responds to this dominance. There is never a need for the type of aquatic locomotor total pattern which is found in the iishes and amphi«bians.

Early Reflexes in Mammalian Embryos

True behavior makes its appearance about one day after it was Erst possible to elicit muscle contractions in embryos of the rat, guinea pig, cat and sheep. It is essential to emp1oy experimental methods which do not impair the physiologic conditions of pregnant animals and their embryos to observe the tirst reflexes. Furthermore, studies must be conducted immediately upon opening the uterus because this operation invariably interferes with placental respiratory exchange, resulting in anoxemia. The procedures used in such studies have been discussed in the first chapter.


Although the description of early reflex responses which follows pertains primarily to cat embryos about 14 mm. crownrump lengthP similar results have been obtained in other mammals. 3,4,6,7 When an embryo with placenta still attached to the uterine wall has been brought quickly into view and the intact amniotic sac is percussed witli some blunt instrument, pressure transmitted to the embryo through the amniotic fluid results in quick outward and backward movement of the forelimb. The movement may be called a twitch or jerk. similar responses are obtainable in other ways. Flipping the limb gently with a needle or a hair passed through the amnion serves equally well. In a few instances it was even possible to elicit this reaction by lightly touching certain points upon the forelimb. Furthermore, faradic shocks applied to approximately the same points by means of micro-electrodes gave rise to similar quick outward and backward movements of the limb.


Another reaction is frequently elicitable in embryos 14 mm. long. stimulation of the forward end of the head. especially the snoutz results in extension of the head. When the stimulus is applied to one side ok the midline the head moves toward the opposite side and baclcwardH When the tip ok the snout is stimu1ated it moves baclcward. Because this head response is more resistant to changing physiologic conditions than that of the korelimb it usually persists a little longer. Under the best conditions it too is a quiclc movementz It has been observed by all investigators, although some have encountered it at an earlier stage than others.


The head and forelimb responses are entirely separate and distinct from one another when they iirst appear. They difker somewhat in respect to the types of stimulation eliciting them but both seem to require stronger stimuli at first than they do at a slightly later stage in development. The head movements, being contralateral and involving muscles some little distance away from the site of stimulation, are certainly reflexes. All observers agree on this point. However, some have doubted the reflex nature ok the korelimb reactions, holdingsthat they may be due to stimulation ok the muscles directly. The evidence, which will be reviewed brieilyy kavors the view that they too are simple spinaltype reflexes.


Although the limb muscles can be induced to contract by direct stimulation in asphyxiated embryos, the response held to be a reflex is (a) elicitable kor only a briek interval (okten only a kew seconds) while« metabolic conditions ok the embryo are at their best. states of anoxemia set up experimentally make it impossible to obtain the reactions. Akter adequate direct stimulation the new muscle tends to relax slowly, whereas the reflex-like response (b) seems to be a quiclcer movement with more rapid relaxation. Embryonic muscle appears to respond instantaneously to directly app1ied stimuli, but (c) there is an interval just perceptible between stimulus and response ok thexeiiex type. 0ne muscle contraction after another can be induced by direct stimulation, but (d) a second reflezklilce reaction cannot be made to kollow the Erst one until a briek interval ok time, a rekractory or katigue period, has elapsed. Finally, (e) the responses believed to be reilexes are stereotyped and do not show the molding characterizing direct contractions when the position ok the stimulus is varied.


Other experimental evidence demonstrates that the korelimb movements are reflexes. When xtiicroelectrodes are used to stimulate an embryo over the spinal cord some distance caudal to the forelimb, the same quiclc outward and baclcward twitch results. This is due to conduction up the spinal cord; stimuIation of other parts of the embryo, equally distant from the limbs, does not produce this movement. At least one synapse is involved as indicated in Fig. 53.


Fig. 53. Diagram illustrating the probable nervous elements involved in elicits ing forelimb movement by faradic stimulation of the spinal cord of an early mammalian embryo.


The conception of the refiex nature of the early forelimb response iinds further confirmation in histologic studies in the spinal cords and peripheral nerves of the very specimens which showed the reaction and which were subsequently stained by the Ranson pyridine-silver techniquekss THE All nervous elements essential for reflex action are present in the embryonic spinal cord but their intrinsic synaptic connections are incomplete at the time muscles can be made to contract by stimulating them directly and previous to the appearance of the reliexdilce responses. 0ne iinds alferent neurons whose peripheral Ebers pass to the tissues immediately beneath the' epithelium of the forelimb and whose central branches constitute the dorsal roots and dorsal funiculus of the spinal cord. The efkerent neurons are assembled in two groups in the ventral gray matter of the spinal cord, a medial nucleus for trunk innervation and a lateral nucleus for the arm. The efferent axons courses into the muscles of the shoulder region and end in simple terminations upon some of the muscle übers. Commissural and associationa1 neurons are present in the dorsal column. ,The former are numerous in the region just beneath the dorsomedial border of the dorsa1 funiculus, while the latter tend to accumulate nearer the ventrolateral border of this afferent pathway. Commissural axons pursue a course ventrally through the gray matter and cross the kloor p1ate, to become an ascending tract close to the motor nerve cells which supply the trank. Associational axons pass close to the motor nucleus for limb muscles and enter the Iateral funicu1us. This relation of associational neurons and primary motor forelimb neurons appears to be very intimate, with axons of the former coursing parallel with dendrons of the latter. However, up to the time of appearance of the forelimb response there is no close re1ationship between the primary afferent and the secondary neurons (Fig. 54) . A few collatera1 branches of dorsal funiculus fibers do pass for a very short distance toward the associational group, but not many have reached it.



Fig. 54. Photo1nicrograph of the fifth cervical Segment of the spina1 cord of a 13 mm. cat embryo just before the time the Erst forelimb reflexes can be elicitedx as» Ventral funiculus; tut» association neurons; c» cornmissurex ern» Commissural neurons; ihn, dorsal root and ganglionx M» Iateral funiculusx m.l., motor nucleus for the limb muscles; Max» motor nucleus for the trunlc musclesz p.f., dorsal funiculus. Compare with Fig. 56. Pyridinesjlver stainz x 80.


In the early motile embryos in which reilezklike twitches of the forelimb occurred when the limbs were flipped or when the amniotic sac was percussed, connections have been comp1eted be— tween the primary afkerent and the associational neurons. This accomplished when collateral branches grow in among the cells of the dorsal gray horn from the sensory Hbers nearest the lateral border of the dorsal funiculus Some of the longest collaterals enter the nucleus of motor cells supplying the forelimb musc1es. These relationships will be seen in accompanying photomicros graphs (Figs. 54 and 55) and diagrams (Figs. 56 and 57) . The organization of the first structural reflex mechanism is clearly such that when it begins to kunction the response will not only be homolateraI but will be conlined to the segments at which the impulses enter the spinal cordx The greatest number and the longest new collaterals first grow into the gray matter in the brachial region and, correlatively, one linds the first reflex response involving the forelimbs.


Fig. 55. Photoicrograph of the dorsal funiculus (zt).j.) f the spinal cord of: a 13 mm. cat embryo showing the Erst collateral branches (col.) of primary aikerent neuronsz these serve to complete the first spinal reflex arcs. Pyridine-silver stain x 510.


Fig. 56. Camera lucida tracings ok the dorsal roots (d.s·.) and dorsal kuniculus (d.f.) ok sheep embryos M) Do mai» (B) 23 kam» and (c) 24 nun. long. The developrnent ok collaterals (col.) ok the dorsal kuniculus which curve rnedially around the gelatinous substance (gel.) ok the gras matter is correlated with the appearance ok the tirst korelitnb retiexes. Pyridine-silver stainz X 72.


Fig. 57. Diagrammatic cross Section through the embryonic spinal cord just before (lekt side) and just after (right side) the completion ok reilex arcs malte the earliest retiexes e1icitable. The earliest connections ok aiketent neurons (·a) appear at the lateral end ok the dorsal kuniculus and complete unisegtnental reklex arm. some ok these involve an interneuron but others (c) make direct connections with the pritnary motor neurons kor the limb rnuscles. Only later do the dorsal kuniculus übers krom lower segtnents ok the spinal cord connect with the Commissural interneurons by means ok collaterals O) and thus etkect contralateral trunk movements.



The correlation between completion of anatomical reflex arcs in the spinal cords of cat embryos and the manifestation of forelimb reiiex function has been confirmed in the chiclc, rat and sheep. The stage of development reached in the spinal cord of these four species at the time reiiexes appear varies to some extent, but the responses occur in all at the time reflex arcs are ready irrespective of other structural variations.


such evidence as has been disclosed by the correlated histologic and physiologic experiments reviewed here briefly leads to the conclusion that the early foreIimb movements are local, uni— segmentah homolateral two- and three—neuron reflexes. Mammalian behavior has its genesis, not in a mass reaction or total pattern like that of lower vertebrates, but in these relatively Simple reilexes which are at first entirely nonintegrated.

Other Siuple Reflexes and Their Integration

During the course of development of cat embryos, many re— flexes malte their appearance. Just as the first responses at the shoulder can be elicited before the limbs move spontaneously and before they move with the neclc and trank, local reilexes appear at the elbow and wrist joints as separate entities before the distal portions of the« limbs become integrated with other parts of the body. Local flexion at the elbows occurs at about the 16—mm. steige. It is often followed by other more distant movements, such as bending at the shoulder or extension of the head and flexion of the trunk. However, these more proximal and cephalic movements are not followed by rnovement at the elbow at this time. similarly, local wrist movements seen in embryos about 17 mm. long, are at first unrelated to other movements.


Local movements at the proximal hind-leg joint, unintegrated with trunlc responses, are encountered in specimens between 15 and 16 mm. long. Those at the lcnee appear at 17.5 mm. The earliest independent motility of the tail is found at the same stage.


Although the first head reilexes can be elicited by stimulating only a small area near the tip of the snout in embryos 13—14 mm. long, it is but a short time later that they occur in response to stimulation of most of the facial area. In specimens 15—16 mm. long, contralateral head flexion is obtainable from all parts of the face except that supplied by the ophthalmic division of the trigem— inal nerve. From the ophthalrnic region, extension with flexion to the same side occurs. With further developmenh stimulation of more and more Portions of the face leads to the homolateral response until, at about the 20 mm. stage, only the ear gives a contralateral head flexion.


These and other interesting reflex sactivities have been ob— served in embryos. All possess an element of individuality at first, but ultimately most of the local responses are brought together into more generalized movements. This comes about by integration within the frameworlc of a growing central nervous mechanism. Longitudinal tracts of nerve ftbers develop within the spinal cord, and as they make connections with afkerent and efkerent neurons they begin to exert an integrating function over the local, isolated reactions.


The earliest secondary pathway in the spinal cord is a ventral longitudinal bundle, primarily an ascending tract formed by the axons of commissural neurons. Impulses carried by it apparently are able to discharge motor neurons supplying trunk and neck musc1es at more rostral 1evels. Cel1 bodies of the commissural neurons, lying near the medial border of the dorsal funiculus, receive impulses from primary afferent neurons which have been coursing rostrally for some distance in the dorsal funiculus. Consequently the local homo1ateral forelimb reflex is sometimes followed, at the 15 to 1 6 mm. stage, by a contraction of neclc muscles similarly at a later period, hind-limb reflexes are followed progressively by responses of the forelimbs and the neck. A progressive discharge of neurons from caudal to rostral regions of the spinal cord is broughtlabout through integration of ascending neurons of the primary afferent dorsal funiculus with the commissural secondary tract.


Nerve fibers grow caudally into the spinal cord from centers in the medulla oblongata and midbrain. Many of these occupy positions in the ventral funiculus but they do n’ot reach any given point in the spinal cord until after ascending Ebers from a lower spinal segment have reached the medulla oblongata. consequently stimulation of structures near the caudal end of an embryo of about 18 mm. (Fig. 58) can result sequentially in (a) local reflexes, (b) reflexes of more rostral .parts, (c) head movements and then (d) the trunk activities which are integrated with the head and which always fall just short of the most recently acquired local responses. The descending integrating tracts of nerve ftbers are so placed in the ventral portion of the spinal cord that when activated they can more eifectively bring about discharge of motor cells which supp1y the trunk muscles than neurons for the limb muscles. As a result of such an arrangement the limhs seem not to be completely integrated with the trunk during the early embryonic period. Later the association becomes more intimate. 0n the other hand, the trunlc movements become integrated with those of the neclc almost as soon as they begin to appear at the 15 mm. stage. With growth in size of the individual, more and more muscles of the back are added to the trunk activities in a caudal1y expanding Progression.


Fig. 58. Cat embryo 18.5 mm. C. R. 1ength, from which local reHexes as well as early integrated movements could be elicited. Magniiication is the same as that in Figs. 44 and 47.



Some recent experiments involving the production of states of anoxemiaU have added important information to our conception of the relation of simple reHexes to the more massive integrated activities of cat embryos. When decerebrate cats were allowed to breathe atmospheres low in oxygen before the uterus was opened it was found that local reflexes became depressetd and the integrated head and trunk movements were exaggerated and more sustained or tonic than normally. Irritability of the embryos wss diminished during anoxemia. Extended use ok the gas mixture brought about more complete anoxemia and all responses ceased. spontaneous movements and responses to stimulation ok embryos studied under conditions ok partial anoxemia resemble mass reactions and might easily lead one to the conclusion that behavior develops in mammalss in a manner very similar to that in the Salamander. Only when such conditions are avoided can the various simple reflexes be observed as separate elements.

References Cited

i. swenson, E. A. i9e6. Thesis, Univ. Kansas.

e. Angulo y Gonzalez A. W. i93e. comp. Neur., ss: 39s.

z. Raney, E. T. sc L. carmichaeL i934. Genetic Psychol., 4s: Z.

4. Windle, W. F., W. L. Minear, M. F. Austin sc D. W. 0rr. i93s. Physiol.

Zool» s: i s6.

s. carmichaels L. i934. Genetic Psychol. Mono., is: 337.

6. Bridgmaix c. s. sc L. cariiiichaeL i93s. J. Genetic Psychol., 47: e47. 7. Barcrokh J» D. H. Bari-on sc W. F. Windle. i936. J. Physiol» s7: 73. s. Barcroktz sc D. I-I. Barron. i939. comp. Neur., 7o: 477.

9 o

. Windle, W. F. sc A. M. Griklin. i93i. J. comp. Neur., se: i49. . Windle, W. F., J. E. 0’Donnell sc E. E. Glasshagle i933. Physiol. Zool.,

6- sei.

ii. Windle, W. F., D. W. 0rr sc W. L. Minear. i934. Physiol. Zool» 7: 6oo. ie. Windle, W. F. sc R. F. Becken i94o. Arch. Neun Psychiat., 43: ge.

i Z. coronios, J. D. i933. Genetic Psychol. Mono., i4: es3.

i4. Minlcowslti. M. i93s. Abderhaldecks Handb. biol. Arbeitsmeth, Abt. V,

Teil sB: si i.

is. I-Iooker, D. i936. Yale J. Biol. Med., s: s79.

i6. Preyeix W. isss. specielle Physiologie des Embryo. Stichen, Leipzig. i7. Pankratz D. s. i93i. Anat. Rec., 49: 3i.

is. coghilh G. E. i9e9. Anatomy and the Problem ok Behavioic Macmillan, New York.

i9. Tracy, I-I. C. i9e6. J. comp. Neur., 4o: es3.

eo. Tuge, H. i93i. Proc. soc. Exp. Biol. sc Med., e9: se.

ei. Kuo, Z. Y. i93e. J. Expen Zool» Si: 39s.

ee. Youngstrom, K. A. i93s. J. comp. Neur., 6s: 3si.

es. East, E. W. i93i. Anat. Rec., so: eoi.

e4. clarlc E. L. sc E. R. Clarlh igi4. J. Exp. Zool» i7: 373.

es. 0rr, D. W. sc W. F. Windle. i934. J. comp. Neur., 6o: e7i.

es. Windle, W. F. i939. Physiol. Zool» ie: 39.

e7. Angulo y Gonealez A. W. i933. Proc. soc. Exp. Biol. sc Med., zi- ii»i. es. Windle, W. F. i937. 1bid., Zö- 64o.

e9. scharpenberg, L. G. sc W. F. Windle. ig3s. Anat» 7e: 344.

so. carmichaeL L. i933. 1n C. Murchison’s I-Iandb. child Psychol» end ed»

chap. e, P. 3i, clarlc Univ. Press, Worcestetx Mass

3i. coghilh G. E. i9e9. Arch. Neun sc Psychiat., ei: 989. GENEsIs OF FUNCTION IN NERVOUS sYsTEM 157

ge. Minlcowslch M. 1922. Schweiz. mecL Woche-weht» He: 721, 751. 33. Windle, W. F. 1934. J. comp. Neun, 59: 487.

34. Windle, W. F. 8c D. W. Ort. i934. Ibid., so: 287.

35. Winde, W. F. sc R. E. Bauer. 1936. Ibic1., Eis: 189.

36. Winde, W. F. 8c J. E. Finger-sich i937. Ibid., 67: 493.

37. Angulo y Gonzalez A. W. 1939. Ibic1., 71: 325.


Cite this page: Hill, M.A. (2024, April 24) Embryology Book - Physiology of the Fetus 10. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Physiology_of_the_Fetus_10

What Links Here?
© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
Retrieved from ‘https://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Physiology_of_the_Fetus_10&oldid=352965’
Powered by MediaWiki