UNSW Embryology

Development of the Organs of Audition and Equilibrium

Central Pathway

© Dr Mark Hill (2009)

Acknowledgements

Introduction

Peripheral Hearing Anatomy	Central Auditory Pathway

The this page introduces the central neural pathwat of hearing and balance beginning with the Vestibulocochlear Nerve (crainial nerve VIII) through to the auditory cortex.

Page Links: Introduction | Some Recent Findings | Central Auditory Pathway | Cranial Nerve VIII | Historic Pathway Images | Development Timing | Brainstem Auditory Evoked Response | Abnormalities | Development Overview | References | Glossary

Related Pages: Inner Ear | Middle Ear | Outer Ear | Central Pathway | Abnormalities | Stage 13/14 | Stage 22 | Stage 22 Selected | Molecular | Week 4 Placode Development || Head Notes | Face Notes | Neural Notes

Some Recent Findings

Jiang ZD, Xiu X, Brosi DM, Shao XM, Wilkinson AR. Sub-optimal function of the auditory brainstem in term infants with transient low Apgar scores. Clin Neurophysiol. 2007 May;118(5):1088-1096.

Jiang ZD, Yin R, Wilkinson AR. Brainstem auditory evoked responses in very low birthweight infants with chronic lung disease. Eur J Paediatr Neurol. 2007 May;11(3):153-9.

Search PubMed: auditory neural pathway development | auditory cortex development |

Central Auditory Pathway

 

(Image modified from: Semin Fetal Neonatal Med. 2006 Dec;11(6):444-51.)

Cranial Nerve VIII

The Acoustic Nerve (cranial VIII) consists of two main nerves, roots or parts: cochlear (hearing) and vestibular (equilibrium).

Cochlear Nerve - arises from bipolar cells in the spiral ganglion of the cochlea. Peripheral fibers end in the organ of Corti and the central fibers bifurcate and enter the cochlear nucleus.

Vestibular Nerve - arise from the bipolar cells in the vestibular ganglion (Scarpa’s ganglion). Peripheral fibers end in the semicircular canals, the saccule and the utricle, the end-organs concerned with mechanism for the maintenance of bodily equilibrium.

(Text: modified from Gray's Anatomy)

Historic Pathway Images

	1. Cochlear nerve, with its two nuclei. 2. Accessory nucleus. 3. Tuberculum acusticum. 4. Vestibular nerve. 5. Internal nucleus. 6. Nucleus of Deiters. 7. Nucleus of Bechterew. 8. Inferior or descending root of acoustic.	9. Ascending cerebellar fibers. 10. Fibers going to raphé. 11. Fibers taking an oblique course. 12. Lemniscus. 13. Inferior sensory root of trigeminal. 14. Cerebrospinal fasciculus. 15. Raphé. 16. Fourth ventricle. 17. Inferior peduncle. Origin of striæ medullares. (Testut.)

Brainstem Auditory Evoked Response

The Brainstem Auditory Evoked Response (BAER), also called the BrainStem Evoked Response (BSER) or Auditory Brainstem Response (ABR), techinique is a non-invasive method of determining audiory function and brainstem integrity. The method relies upon computer analysis of neurological responses following a regularly repeated stimulus stream.

Development

26 weeks - human brainstem auditory pathway is anatomically formed.

28 weeks - BAER can be recorded.

less than 34 weeks - latencies of BAER components (I, III, and V) decrease as a function of gestation

BAER Abnormalities

The normal neonatal BAER is altered by a number of different conditions including:

Sensorineural hearing loss

Perinatal asphyxia

Neonatal chronic lung disease (CLD)

Brain haemorrhages and hydrocephalus

Trisomy 21 (Down's syndrome)

Maximum Length Sequence (MLS) - patterned stimulus presentation rather than the uniformly spaced stimuli of conventional BAER

(Data from: Wilkinson AR, Jiang ZD. Brainstem auditory evoked response in neonatal neurology. Semin Fetal Neonatal Med. 2006 Dec;11(6):444-51.)

American Speech-Language-Hearing Association Hearing Assessment

Search PubMed: Brainstem Auditory Evoked Response | Neonatal Brainstem Auditory Evoked Response

Links: Medline Plus BAER - brainstem auditory evoked response | Infant test/procedure preparation | American Speech-Language-Hearing Association Hearing Assessment | Audiological Assessment of Children Birth to 5 Years of Age: 2004 (PDF Format)

Stage 22 Embryo

Historic Images

Left	Ca

Development Timing

Week 3 - otic placode, otic vesicle

Week 5 - cochlear part of otic vesicle elongates (humans 2.5 turns)

Week 9 - Mesenchyme surrounding membranous labrynth (otic capsule) chondrifies

Week 12-16 - Capsule adjacent to membranous labrynth undegoes vacuolization to form a cavity (perilymphatic space) around membranous labrynth and fills with perilymph

Week 16-24 - Centres of ossification appear in remaining cartilage of otic capsule form petrous portion of temporal bone. Continues to ossify to form mastoid process of temporal bone.

3rd Trimester - Vibration acoustically of maternal abdominal wall induces startle respone in fetus.

(These are Human embryonic timings, not clinical which is based on last menstral period +2 weeks)

3 Sources:

Inner ear - epidermal otic placode at level of hindbrain.

Middle ear - cavity: 1st pharyngeal pouch, ossicles: mesenchyme 1st and 2nd pharyngeal arches.

Outer ear - external auditory meatus: 1st pharyngeal cleft, auricle: 6 hillocks 1st and 2nd pharyngeal arches.

Abnormalities

Search PubMed: Preauricular Sinus

Acoustic neuroma
Central pontine myelinolysis

Developmental Overview

Development of Hearing - 3 divisions of ear

• outer
  • external auditory meatus (ear canal)
  • functions to collect sound and gude it to the tympanic membrane
• middle
  • tympanic cavity
  • functions to convert sound pressure waves into mechanical waves of typanic membrane
  • ossicles reduce amplitude but increase force to drive fluid-filled inner ear
  • eustacian tube allows equalization of pressure (into oral cavity)
• inner
  • duct system
  • functions to convert hair displacement into neural signals
  • cochlear (sound)
  • semicircular canals (balance)
  • vestibulocochlear nerve
  • Organ of Corti
  • Hair Cells

Pinna- Auricle

• develops from six aural hillocks
• 3 on first arch
• 3 on second arch
• originally on neck, moves cranially during mandible development

Outer- external auditory meatus

• derived from first pharyngeal cleft
• ectodermal diverticulum
• week 5
• extends inwards to pharynx
• until week 18 has ectodermal plug
• plug forms stratified squamous epithelia of canal and outer eardrum
• Outer Ear Genes
  • controlled by genes that regulate arch 1 and 2 development
  • related to hindbrain segmentation (rhombomere 4)
• Mouse
  • Hox a1/Hoxb1, goosecoid, Endothelin1, dHAND

Middle- tympanic cavity

• derived from first pharyngeal pouch
• extends as tubotympanic recess
• during week 5 recess contacts outer ear canal

mesoderm between 2 canals forms tympanic membrane

expands to form tympanic recess

stalk of recess forms eustacian tube

pharyngotympanic tube

Middle- Ossicles

• develop from first and second pharyngeal arches
• tympanic cavity enlarges to incorporate
• coats with epithelia

first arch mesoderm

• tensor tympani muscle
• malleus and incus

second arch mesoderm

• stapedius muscle and stapes

Middle Ear Genes

• gooscoid, RARs, Prx1, Otx2, Hoxa1, Hoxb1, endothelian related molecules

Inner- otocyst

• week 3 otic placode forms on surface ectoderm
• otic placode sinks into mesoderm
• forms otocyst (otic vesicle)
• Otic Vesicle to Labyrinth 1
• Pig stage 13/14 Otocyst
• Otocyst
• branches form and generate endolymphatic duct and sac
• forms vestibular and cochlear sac

Vestibular sac

• generates 3 expansions
• form semicircular ducts
• remainder forms utricle
• epithelia lining generates
• hair cells
• ampullary cristae
• utricular macula

Otic Vesicle to Labyrinth

• Human Stage 22
• Vestibular- Otoconia
• Otoconin- inner ear biominerals

Cochlear sac

• generates coiled cochlear duct
• humans 2 1/2 turns
• remainder forms saccule
• epithelia lining generates
• hair cells
• structures of organ of corti
• saccular macula
• Human Stage 22- cochlear
• Human Stage 22- cochlear

Bony Labyrinth

• formed from chrondified mesoderm
• Periotic Capsule
• mesenchyme within capsule degenerates to form space filled with perilymph

Vestibulocochlear Nerve

• forms beside otocyst
• from wall of otocyst and neural crest cells
• bipolar neurons
• vestibular neurons
  • outer end of internal acoustic meatus
  • innervate hair cells in membranous labyrinth
  • axons project to brain stem and synapse in vestibular nucleus
• cochlear neurons
  • cell bodies lie in modiolus
  • central pillar of cochlear
  • innervate hair cells of spiral organ
  • axons project to cochlear nucleus

Inner Ear Genes

• hindbrain segmentation occurs at same time placode arises
• otocyst adjacent to rhombomere 5
• may influence development
• Hoxa1, kreisler, Fgf3
• genes regulating neural crest cells (neural genes)
• Pax2 Ko affects cochlear and spiral ganglion, but not vestibular apparatus
• nerogenin 1 affects both ganglia

Semicircular canal

• Otx1- cochlear and vestibular normal

Hmx3, Prx1, Prx2

Sensory Organs

• thyroid hormone receptor beta
• Zebrafish-mindbomb mutant
  • excess hair cells but not supporting cells
    • Notch-Delta signaling

Gene Expression-inner ear

• Brn-3c and Hair cell development
• Supporting Cells- p27kip
• Thyroid Hormone
• Ganglion neurons require growth factors
• vestibular neurons- BDNF, NT3
  • survival not development

Congenital Deafness

• conductive- disease of outer and middle ear
• sensorineural- cochlear or central auditory pathway

Outer ear Malformation

• rare meatal atresia
• canal narrow or not formed
• part of first arch syndrome

Middle ear Malformation

• also rare
• can be part of first arch syndrome
• malformed maleus or incus
• congenital fixation of stapes
• stapes anchored to oval window
• annular ligament fails to develop

Congenital malformations Statistics

Congenital sensorineural

• hereditary or acquired
• see recent reviews

Hereditary

• recessive- severe
• dominant- mild
• can be associated with abnormal pigmentation
• hair and irises

Acquired

• rubella (German measles)
• maternal infection during 2nd month of pregnancy
• vaccination of young girls
• streptomycin
• antibiotic
• thalidomide

Conductive Hearing Loss

• produced by otitis media with effusion, is widespread in young children.
• temporary blockage of outer or middle ear
• See also: recent Ref and Senses WWW Link

Human Genes

LocusID Symbol Description Position Links 1678 DFN1 deafness, X-linked 1, progressive Xq22 1679 DFN2 deafness, X-linked 2, perceptive, congenital Xq22 1680 DFN4 deafness, X-linked 4, congenital sensorineural Xp21.2 1701 DFNB9 deafness, autosomal recessive 9 2p23-p22 1729 DIAPH1 diaphanous (Drosophila, homolog) 1 5q31 2706 GJB2 gap junction protein, beta 2, 26kD (connexin 26) 13q11-q12 4647 MYO7A myosin VIIA (Usher syndrome 1B (autosomal recessive, severe)) 11q13.5 5459 POU4F3 POU domain, class 4, transcription factor 3 5q31

Conductive Hearing Loss

• Conductive Hearing Loss Produces a Reversible Binaural Hearing Impairment David R. Moore, Jemma E. Hine, Ze Dong Jiang, Hiroaki Matsuda, Carl H. Parsons, and Andrew J. King J. Neurosci. 1999;19 8704-8711
  • http://www.jneurosci.org/cgi/content/abstract/19/19/8704
  • tested ferrets by lon-term plugging of ear canal
  • Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking.
  • Results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss.
  • Show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.

References

Molecular Normal Development

•  Jones JM, Montcouquiol M, Dabdoub A, Woods C, Kelley MW. [See Related Articles]  Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Corti. J Neurosci. 2006 Jan 11;26(2):550-8.
•  Kawamoto K, Ishimoto S, Minoda R, Brough DE, Raphael Y. [See Related Articles]  Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo. J Neurosci. 2003 Jun 1;23(11):4395-400.
•  Zine A, de Ribaupierre F. [See Related Articles]  Notch/Notch ligands and Math1 expression patterns in the organ of Corti of wild-type and Hes1 and Hes5 mutant mice. Hear Res. 2002 Aug;170(1-2):22-31.

List of recent Ear Development Reviews

Recent Reviews Abnormal Development

•  Webster WS. [See Related Articles]  Teratogen update: congenital rubella. Teratology. 1998 Jul;58(1):13-23. Review. PMID: 9699240; UI: 98364396.
• Yates JA, et al. [See Related Articles] Isolated congenital internal auditory canal atresia with normal facial nerve function. Int J Pediatr Otorhinolaryngol. 1997 Jul 18;41(1):1-8. Review.PMID: 9279630; UI: 97425580.
• Lambert PR, et al. [See Related Articles] Congenital malformations of the external auditory canal. Otolaryngol Clin North Am. 1996 Oct;29(5):741-60. Review. PMID: 8893214; UI: 97048378.
• Lin AE, et al.  [See Related Articles] Further delineation of the branchio-oculo-facial syndrome. Am J Med Genet. 1995 Mar 13;56(1):42-59. Review. MID: 7747785; UI: 95266633.
• Strasnick B, et al  [See Related Articles] Teratogenic hearing loss. J Am Acad Audiol. 1995 Jan;6(1):28-38. Review. PMID: 7696676; UI: 95210704.
• Kossowska E, et al. [See Related Articles] Prenatal and neonatal prophylaxis in otorhinolaryngology. Int J Pediatr Otorhinolaryngol. 1980 Jun;2(2):85-98. Review. PMID: 6765128; UI: 84160924.
• Gottlieb G. [See Related Articles] Conceptions of prenatal development: behavioral embryology. Psychol Rev. 1976 May;83(3):215-34. Review. No abstract available.
  PMID: 188059; UI: 77079452.
• Holme RH, Steel KP Genes involved in deafness. Curr Opin Genet Dev 1999 Jun;9(3):309-314
  • Remarkable progress has been made over the past few years in the field of hereditary deafness. To date, mutations in at least 35 genes are known to cause hearing loss. We are now beginning to understand the function of many of these genes, which affect diverse aspects of ear development and function.

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