Download Cochlear anatomy, function and pathology I

Cochlear anatomy, function and
pathology I
Professor Dave Furness
Keele University
[email protected]
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 membraneous
labyrinths
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
3 week old mouse
8 week old guinea pig
Left: Mahendrasingam et al., 2011, JARO; Right Hackney and Furness, Noise and its Pathophysiology
(eds Luxon and Prasher, 2007, Wiley)
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
Increasing
mass
Low frequencies
Basilar membrane and
organ of Corti
High frequencies
Increasing
stiffness
cochlear
nerve
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
Stria
vascularis
tectorial
membrane
Nerve
fibres
From Furness and Hackney, Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery 7
The reticular lamina by scanning electron
microscopy
OHC
IHC
The reticular lamina by scanning electron
microscopy
OHC
IHC
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 epithelium
Cochlea +
organ of Corti
Inner hair
cells
Outer hair
cells
Comparing the inner and outer
hair cells
IHCs flask shaped; mitochondria
dispersed; nucleus central
OHCs 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)
0
0
minus (inhibition)
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 the
tip link
A model of mechanosensitivity
A 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
+80 mV
-70 mV
response
stimulus
Glutamate transporters around IHCs but not
OHCs confirm glutamatergic transmission
Inner
phalangeal
cells around
IHCs
OHC area
Fibrocytes
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