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![Page 1: Cochlear anatomy, function and pathology I - UConn Health · Cochlear anatomy, function and pathology I Professor Dave Furness Keele University d.n.furness@keele.ac.uk](https://reader030.fdocuments.in/reader030/viewer/2022040700/5d522a4a88c993a1398bb518/html5/thumbnails/1.jpg)
Cochlear anatomy, function and pathology I
Professor Dave FurnessKeele University
![Page 2: Cochlear anatomy, function and pathology I - UConn Health · Cochlear anatomy, function and pathology I Professor Dave Furness Keele University d.n.furness@keele.ac.uk](https://reader030.fdocuments.in/reader030/viewer/2022040700/5d522a4a88c993a1398bb518/html5/thumbnails/2.jpg)
Aims and objectives of these lectures
• Introduction to gross anatomy of the cochlea
• Focus (1) on the sensory epithelium:– Hair cells and the organ of Corti– The mechanism of mechanoelectrical
transduction
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Aims and objectives of these lectures
• Focus (2) on the biophysics of the cochlea, the dual roles of hair cells and their innervation:– Cochlear frequency selectivity– The cochlear amplifier– Neurotransmission and innervation of the
hair cells– Spiral ganglion and the structure of the
auditory nerve
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Aims and objectives of these lectures
• Focus (3) on the cochlear lateral wall and Reissner’s membrane:– The spiral ligament– The stria vascularis
– The endolymphatic potential and potassium recycling
– Reissner’s membrane
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Aims and objectives of these lectures
• Focus (4) on cochlear pathology:– Presbyacusis– Ototoxicity– Noise trauma– Genetic hearing loss– Molecular mechanisms of cell loss– Regeneration and repair
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Inner ear
From Bear, Connors and Paradiso, Neuroscience: exploring the brain (Lippincott Williams and Wilkins)
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Cochlea• The main functions of the cochlea are to
analyse and convert the vibrations caused by sound into a pattern of electrical signals that can be conveyed along the auditory nerve fibres to the brain
• This process involves three main steps:– sensory transduction– processing of the signal– neurotransmission
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The bony and membraneouslabyrinths
From Furness and Hackney, Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery 7
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scala vestibuli
scala media
scala tympani
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Cross sections of the cochlear duct
Left: Mahendrasingam et al., 2011, JARO; Right Hackney and Furness, Noise and its Pathophysiology (eds Luxon and Prasher, 2007, Wiley)
3 week old mouse8 week old guinea pig
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Fluid segregation
• The three chambers contain different fluids• Endolymph, high in potassium, in scala
media
• Perilymph, high in sodium, in scala
vestibuli and scala tympani
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The cochlea is a frequency analyser
Low frequencies
High frequencies
Basilar membrane andorgan of Corti
cochlear nerve
Increasingmass
Increasingstiffness
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Frequency mapping on the basilar membrane
• Discovered by Georg von Békésy who was awarded the Nobel Prize for Physiology or Medicine, 1961
• Used human cadavers and played sounds to them, whilst observing the motion of the basilar membrane
• Measured the travelling wave and noted peaks of tuning
• However, the peaks were not sharp enough to account for human frequency selectivity
• Active physiological mechanisms are also required
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Frequency analysis in the cochlea• Sound sets up a travelling wave along the
basilar membrane• The peak of motion determines the frequency
selectivity (tuning) of the cochlea at that point• The peak moves further along as frequency
gets lower
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Basilar membrane animation
YouTube video Copyright: Howard Hughes Institute (under license)
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Cross sections of the cochlear duct
From Furness and Hackney, Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery 7
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Organ of Corti• Organ of Corti consists of a sensory epithelium with
hair cells and supporting cells
Nervefibres
Striavascularis
tectorial membrane
From Furness and Hackney, Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery 7
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The reticular lamina by scanning electron microscopy
IHCOHC
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The reticular lamina by scanning electron microscopy
IHCOHC
Supporting cells: inner pillar, outer pillar, Deiter’s cell 1, Deiter’s cell 2, Deiters cell 3.
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Supporting cells are rich in actin and tubulin (cytoskeletal proteins) to provide mechanical support to the organ of Corti
From Furness and Hackney, Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery 7
![Page 23: Cochlear anatomy, function and pathology I - UConn Health · Cochlear anatomy, function and pathology I Professor Dave Furness Keele University d.n.furness@keele.ac.uk](https://reader030.fdocuments.in/reader030/viewer/2022040700/5d522a4a88c993a1398bb518/html5/thumbnails/23.jpg)
Supporting cells are rich in actin and tubulin (cytoskeletal proteins) to provide mechanical support to the organ of Corti
From Furness and Hackney, Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery 7
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Immunogold shows sorting of different actin isoforms in different organ of Corti cell types
From Furness et al Hear Res. 2005 Sep;207(1-2):22-34
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Hair cells• Auditory stimuli are received in the form of
mechanical energy• Hair cells are mechanosensory receptors of
the inner ear and are found in the cochlear and vestibular epithelia
• They share common characteristics which underlie their sensitivity to mechanical stimuli
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Hair cells in auditory epitheliumOuter hair
cellsInner hair
cellsCochlea +
organ of Corti
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Comparing the inner and outer hair cells
IHCs flask shaped; mitochondria dispersed; nucleus centralOHCs cylindrical; mitochondria mostly lateral, nucleus basal
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Hair cells in the organ of Corti
• Two types, structurally and functionally distinct
• A number of similarities and differences• Bundle structure – similar rows of
stereocilia but different shapes• Both can perform mechanoelectrical
transduction• Innervation differs between the two
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Overview of bundle structure
• Stereocilia form precise rows
• They are coupled by various extracellular filaments
From Hackney and Furness J Cell Sci 2013; 126(Pt 8):1721-1731
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The hair bundle is the hair cell’s transducing element
• Composed of stereocilia linked together by extracellular filaments
• Contains many different proteins• The core of the stereocilium is actin• It also contains myosins and a variety of
scaffolding and calcium modulating proteins
• Extracellular filaments composed of other proteins
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Other important proteins required for transduction
• Transducer elements– TMC1 (transmembrane
channel 1)– TMC2 (transmembrane
channel 2)– LHFPL5 (TMHS)
(tetraspan membrane protein of hair cell stereocilia)
– Protocadherin 15– Cadherin 23– TMIE (transmembrane
inner ear protein)
• Structural and regulatory components– Harmonin– Sans– Whirlin– Usherin– Stereocilin– EPS8, EPS8L2– PTPRQ– VLGR1– Calmodulin– PMCA2A (calcium
ATPase)
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Links
• The composition of links is becoming better understood
• Their distributions tend to follow a particular pattern
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Hair bundles are the site of mechanoelectrical transduction
• Hair cells are sensitive to deflections of the hair bundle along the axis of sensitivity
plus (excitation)
minus (inhibition)
0 0
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Transduction occurs when the stereocilia are deflected
positive negative
+
--
+
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Hair cell responses
Moving stereocilia
Cell electrical response
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The tip-links
• Excitatory deflections of stereocilia open transduction channels by means of a gating spring
• The spring is represented by thetip link
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A model of mechanosensitivityA single tip link
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Tip links and transduction channels
TMHS
From Hackney and Furness J Cell Sci 2013; 126(Pt 8):1721-1731
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Immunolocalization of TMHS/LHFPL5
Actin (green), TMHS (red)
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Hair-cell transduction and neurotransmission
stimulus
response
+80 mV
-70 mV
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Glutamate transporters around IHCs but not OHCs confirm glutamatergic transmission
Inner phalangeal cells around IHCs
FibrocytesOHC area
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Summary
• In this lecture we have looked at the gross structural anatomy of the cochlea
• We have examined the organisation and function of the organ of Corti
• We have described and explained mechanoelectrical transduction – how the hair cells detect mechanical stimulation