Cochlear anatomy, function and pathology I
Professor Dave FurnessKeele University
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
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
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
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
Inner ear
From Bear, Connors and Paradiso, Neuroscience: exploring the brain (Lippincott Williams and Wilkins)
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
The bony and membraneouslabyrinths
From Furness and Hackney, Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery 7
scala vestibuli
scala media
scala tympani
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
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
The cochlea is a frequency analyser
Low frequencies
High frequencies
Basilar membrane andorgan of Corti
cochlear nerve
Increasingmass
Increasingstiffness
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
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
Basilar membrane animation
YouTube video Copyright: Howard Hughes Institute (under license)
Cross sections of the cochlear duct
From Furness and Hackney, Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery 7
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
The reticular lamina by scanning electron microscopy
IHCOHC
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.
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
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
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
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
Hair cells in auditory epitheliumOuter hair
cellsInner hair
cellsCochlea +
organ of Corti
Comparing the inner and outer hair cells
IHCs flask shaped; mitochondria dispersed; nucleus centralOHCs cylindrical; mitochondria mostly lateral, nucleus basal
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
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
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
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)
Links
• The composition of links is becoming better understood
• Their distributions tend to follow a particular pattern
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
Transduction occurs when the stereocilia are deflected
positive negative
+
--
+
Hair cell responses
Moving stereocilia
Cell electrical response
The tip-links
• Excitatory deflections of stereocilia open transduction channels by means of a gating spring
• The spring is represented by thetip link
A model of mechanosensitivityA single tip link
Tip links and transduction channels
TMHS
From Hackney and Furness J Cell Sci 2013; 126(Pt 8):1721-1731
Immunolocalization of TMHS/LHFPL5
Actin (green), TMHS (red)
Hair-cell transduction and neurotransmission
stimulus
response
+80 mV
-70 mV
Glutamate transporters around IHCs but not OHCs confirm glutamatergic transmission
Inner phalangeal cells around IHCs
FibrocytesOHC area
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