Audition I Exam #2

Osseous (bony) labyrinth of inner ear

-Inner ear includes:

·Cochlea for hearing

·Vestibular apparatus for balance

·Semicircular canals (3-superior, posterior, and lateral) and vestibule (saccule + utricle)

Terminology in Cochlea

-Cochlea contains 3 scalas: scala vestibuli, scala tympani, and scala media (cochlear duct) separated by two membranes

-Pathway between SV and ST at apex: helicotrema

-Location of organ of corti (OC)

-Osseous spiral lamina and BM

-Spiral ganglions (SGNs) in Rosenthal canal: axons and dendrites

-Organization of 8th nerve: (1) frequency configuration, (2) auditory vs. vestibular

Where do high and low frequency fibers go in the cochlear nerve?

-High frequency fibers go from basal turn to peripheral region in the cochlear nerve

-Low frequency fibers go centrally in cochlear nerve

Internal Auditory Meatus Nerve Anatomy

-7up, coke down:

·Facial nerve is located superiorly

·Cochlea nerve is located inferiorly

·Superior vestibular nerve

·Inferior vestibular nerve

3 Scalae, 2 Membranes, and 1 Ligament

-Scala vestibuli (SV) and scala tympani (ST) contain perilymph (similar to extracellular fluid)

-Scala media (SM) contains endolymph (similar to intracellular fluid)

-SV and ST are connected through the helicotrema at the apex of the cochlear canal

-BM (basilar membrane) and RM (Reissner membrane)

-Lateral wall of SM: stria vascularis and spiral ligament

Inner ear lymphatic spaces and connections

-Perilymph space is connected with CSF space through cochlear aqueduct underneath arachnoid membrane

-Black space: endolymph filled space, inside membrane labyrinth

·Connection to endolymphatic sac through a small canal

-The endolymphatic sac is responsible for reabsorption of endolymph

·Blocking it may cause cochlear hydrops and vertigo attack—Ménière's disease)

The coiled turns of cochlea

-At base: wider Osseous spiral lamina, narrower BM

-At apex: narrower Osseous spiral lamina, wider BM

Geometry features for BM vibration

-Effective vibration of BM: up and down

-Acoustic force gets into cochlea at oval window, partially released from round window

-BM up and down to balance the pressure

-This is due to:

·Volume of SV is slightly larger than ST

·Flexibility of round window is higher than oval window

-BM vibrates much larger than bone in displacement

-Osseous spiral lamina vibrates but with very limited displacement

-OC is on BM, not on Osseous spiral lamina

-Therefore, the effective vibration is that of BM

Geometry for Frequency Analysis

-Cochlear duct is larger at basal turn, Osseous spiral lamina wider at base

-However, the BM is narrower at the base

-Different resonant frequencies throughout the cochlea due to gradients of BM:

·Mass

·Stiffness

-Both related to the length (width) and thickness (including the height of OC)

Types of Cochlear Cells

-Hair cells:

·Inner hair cells (IHCs)—one row

·Outer hair cells (OHCs)—three rows

-Supporting cells—contacting hair cells

·Outer/inner pillar cells

·Deiter cells

·Border cells of inner sulcus

·Henson's cells

-Other cells: Claudius C, fibrocytos

Organ of Corti

-One row IHCs, three to four rows of OHCs

-Supporting cells: pillar cells, sulcus cells, Hensen's cell, Deiter's cells

-Tunnel of corti: supported by pillar cells (inner and outer), which are also called rod of corti—used to be thought of as the source of cochlear resonance

-Relationship between supporting cells and hair cells: difference for IHC and OHC

-Relationship between tectorial membrane and stereocilia of IHCs and OHCs

OC: more critical points

-Tight junction around the tops of HCs and supporting cells

-Related structures are reticular lamina and cuticulare plate

-Tight junctions separate endolymph and perilymph

-Tight junction is formed at the level of reticular lamina

-Only the top surface of HCs contact endolymph

-BM is permeable to perilymph

Tectorial Membrane

-Structure to bend stereocilia (located above the HCs)

·Gel protein and fibrous structure

·Physical connection between TM and stereocilia of OHCs, but not IHCs

·The connections make the stereocilia to bend in radial direction when BM moves up and down

·How are the stereocilia of IHC bent?

·Henson's stripe

·Hydraulic coupling

Deiter's cells to OHCs

-Support at the bottom of OHCs

-Processes to the top of OHCs

-Freedom for OHCs

-Longitude connection: limited freedom

Deiter cells (DC) and hair cells (HC)

-DCs are structurally strong

-Transfer BM vibration to hair cells

-The finger of DC goes up to other HCs—making longitude connection

Top surface of OC

-3 rows of OHCs (starting 1 from inside to out)

-DC and OP (outer pillar cells) participate the formation of the reticular lamina: mosaic shape

-Configuration of the stereocilia—difference between IHCs and OHCs: straight line for IHC, and W shape for OHCs

-Three rows of stereocilia: the most lateral row is tallest

IHC versus OHC: contact w/ SCs

-IHC: vase shape, is totally surrounded by SCs

-OHC: cylinder shape, is largely free of direct contact from SCs

OHC

-Cylinder shape

-Bottom location of nuclei

-Thick lateral wall

-Limited contact with SC

-W-shape stereocilia

-Innervation by type II SGNs and medial efferent

IHC

-Vase shape

-Thin lateral wall

-Straight stereocilia

-Middle location of nuclei

-Full contact with SC

-Innervation

Functional connection with anatomy

-Limited contact between SCs and OHCs makes OHCs free of moving (shape change) in response to sound, a feature that is important for OHC function as a mechanical amplifier

-Thick lateral wall makes the OHCs stronger and can stand up with limited support from SCs

-Different innervation: IHCs-SGN (type I) is the main ascending info pathway

Cochlear Innervation

-Afferent:

·Type one to IHCs

·Type two to OHCs

-Efferent:

·Medial eff to OHCs

·Lateral eff to IHCs

-Cochlear pathway: habenula perforata (area of bony spiral lamina pierced with openings for nerve fibers entering OC)—rosenthal's Canal—modiolus—internal auditory meatus

How does cochlea analyze sound frequency?

-3 main theories:

·Place theory by Helmholtz and Bekesy

·Frequency theory by Rutherford

·Place-Volley theory by Waver

Place/Resonance Theory

-First proposed in 1884 by Helmholtz based on his study on resonators. He thought that cochlea = a group of independent resonators of different natural frequencies

-He thought the rod of Corti may be the resonators—based upon the earliest microscopy observation

-This proves to be WRONG

Modern Place Theory

-Proposed by Bekesy based upon his discovery of travelling wave

-Traveling wave theory:

·The sound pressure applied to the oval window is transmitted as a travelling wave along the basilar membrane. The peak displacements for high frequencies are toward the base, and for low frequencies are toward the apex

Traveling Wave

-Direction: base to apex

-Peak location: determined by frequency of sound signal

-Asymmetric: steeper at low frequency side (apex side), broader wave for low frequency signals

-Speeds up first, then slows down towards peak, then faints away over the peak

-Traveling frequency does not equal signal frequency

-Travelling speed << sound speed

Traveling wave by a low frequency tone has:

-Wider envelope (cover larger distance on BM)

-Slower speed

-Peak at apical region

Change of peak location and phase

-Peak location corresponds to the place with quick phase change (or phase lag)

-Phase lag occurs as a function of distance from stapes (due to the increase of mass, BM at apex takes longer to vibrate)

Stiffness and length of string

-Narrower BM and stiffer BM at basal turn

-Shorter string plays higher frequency (similar to musical instrument)

Limitations of Bekesy's Study

-Bekesy failed to detect the active component of BM vibration

·Used dead cochleae

·Poor sensitivity of equipment

·Therefore he needed to use a high intensity of sound (>120 dB SPL)

·Only the passive component of BM vibration was observed

Receptor—a sensory organ

-Basic function (transduction or conversion)

·Signal (type) converting (e.g., sound (a mechanical signal)) to receptor potential of HCs (an electrical signal)

-Basic features

·Specificity—e.g., ears to sound, eyes to light

·Determined by the type of receptor cells as well as accessory (or auxiliary) structure

-Receptor potential vs action potential

·AP: all-or-none impulse

·RP: graded, encode stimulation strength in amplitude

Receptor Specificity

-One receptor is sensitive to ONLY one type of stimulus (signal)

·Sensitivity is not 100% to one particular type of stimulus. Can be responsive to other types of stimuli but with much poorer sensitivity (so usually ignored). Requires a high strength of stimulus to be perceived

-Specificity is determined by the type of receptor cells (e.g., photoreceptors in eyes, and mechanical receptor cells in inner ears)

-Specificity is also determined by the accessory structure—hair cells in cochlea are almost the same as in vestibule, but the two organs respond differently to sound and body movement

Receptor potential

-Definition: the membrane potential of the receptor cells

-Feature: graded (the magnitude associated with the strength of the stimuli)

-Opposite to the action potentials, which are all or none in nature

IHCs as main information pathway in cochlea

-BM vibration

-Deflection of stereocilia of IHCs

-Receptor potential of IHCs

-Action potentials of type I SGNs

-SGN to CAS (central auditory system)

OHCs provide positive feedback—active, mechanical amplification

-BM vibration

-Deflection of stereocilia of OHCs

-Receptor potential—not sure what signal will go from OHCs to brain

-OHC motility (mechanical amplification)

-Feedback as an enhancement to IHC stereocilia

-Responsible for the high sensitivity to sound

-Majority of cases with sensorineural hearing loss will cause significant amounts of OHC loss rather than IHC loss

Macro-versus Micro-vibration

-Macromechanics: BM vibration causes OC to vibrate

-Micromechanics:: vibration of different parts in OC and the interaction among those parts

·OC vibration —> bending of stereocilia —> OHC motion —> enhance BM vibration

·Coupling of BM vibration to IHC receptor potential

Cochlear Conduction

-Stapes —> vibration of inner ear fluid

-BM vibrate as seen in traveling wave

-However, the effective BM vibration occurs up-and-down

Determining factors for BM up/down vibration

1. Different dimensions between SV and ST

2. Different flexibility between OW and RW: RW more flexible

-Because of this, acoustic force is not totally released from oval window to SV via helicotrema, ST and eventually round window. Rather, BM bend up and down to balance the pressure between the two spaces

The manner of cochlear vibration

-The asymmetrical features result in:

·Oval window pushed in (in condensation phase)—BM pushed down

·Oval window drawn laterally (in rarefaction phase)—BM pushed up

-Up-down movement of BM is allowed, and effective stimulus because the two sides of BM are fixed

BM vibration in radial direction: shearing

-Due to the restrain along both sides of BM, the ribbon cannot vibrate freely

-There is a change of vibration amplitude along the radial direction

-The largest vibration occurs at the bottom of outer pillar cells, between pars tecta (from spiral limbus to OP) and pars pectinata (from OP to spiral ligament)

Shearing and Consequence

-OC is relatively rigid, due to the rod of Corti

-The tallest stereocilia of OHCs are connected with TM (tips embedded into it), but rooted in cuticular plate, also a rigid structure

-So rotation causes shearing between TM and reticular lamina

-Other stereocilia are connected to the tallest row by "link"

Hair bending and BM vibration

-Stapes moves out (rarefaction in external ear), BM displaces towards SV (BM moves up): stereocilia (hairs) bend laterally (towards lateral wall of SM)—the direction causing excitation

-Stapes moves in (compression in external ear), BM displaces towards ST, hairs bend centrally (towards modiolus)—the direction causing suppression

Transduction

-Definition: the process of a type of stimuli (acoustical in cochlea) to membrane potential of receptor cells (e.g., HCs in cochlea)

Transduction in Cochlea

-Transduction occurs across hair cells, the receptor cells in cochleae

-Transduction occurs at the level of reticular lamina—related to the bending of hairs

-Transduction is mediated by ion channels on hair cells that are controlled by the bending of the stereocilia

-Transduction requires special biochemistry environment in the cochlea

Perilymph vs Endolymph

-Perilymph: similar to CSF

·Low K, high Na

-Endolymph

·Similar to intracellular fluid in terms of high K, low Na, hyperosmotic

·Not an organic composition

·A special extracellular fluid

·Has a positive potential (endocochlear potential, EP)

-The high K in endolymph is responsible:

·For the formation of EP

·For transduction (the carrier of transduction current)

Special biochemistry environment for HCs

-Endolymph space is bordered by tight junctions along Reissner's membrane, the stria vascularis and along the reticular lamina

-BM is permeable, so that the bodies of HCs are submerged in perilymph, or Corti fluid, which is quite similar to perilymph, not endolymph

-The top of HCs, and stereocilia are soaked in endolymph

-Across organ of Corti, perilymph and endolymph are separated along reticular lamina by tight junction

Potentials between endolymph and intracellular space

-SM: high concentration of K+, positive 80 mV

-Inside hair cells: also high K+, low sodium, -60 mV

-Making the total difference 140 mV

-This potential difference drive K+ from SM to HCs, if the door (MET channels) is opened

Ion movement

-Ions have charges and can be driven by voltage difference

-Ions are particles and can diffuse in liquid (from spot of high concentration to that of low)

-Ion movement is therefore driven by differences in both voltage and concentration

-Some times, the two forces are in the opposite direction, the movement is therefore determined by the net force

Davis's Theory

-Davis correctly predicted the working principle of cochlear transduction

-Two energy pumps in serial connection: one in stria vascularis for EP and the other at the lateral wall of hair cells

-Both pumps provide energy for transductions

-Transduction channels must be K channels and must be located at the top of hair cells

What we know after Davis

1. Transduction occurs at the level of reticular lamina, proved by electrophysiology experiment recording cochlear microphonics

2. Transduction channels are located inside stereocilia and are controlled by the bending of the hairs—tiplink theory

3. The transduction channels allow K+ to pass, but not selective (evidence from exp using radioisotope)

4. The channels are mechanical-electrical transduction (MET) channels (details of the structure and the function)

-Generation and the maintenance of endocochlear potential

K current across MET channel

-MET current is carried by K, although MET channels are open to all positive ions

-K is mainly driven by voltage via MET channels [concentration diff is small]

-K is favoured because:

·Downhill movement, requiring no energy, and then reduce noise [no other positive ions have such feature]

·Less disturbing of intracellular environment due to high concentration of K inside HCs

Standing Current

-When there is no stimulation, MET channels are open partially, at low level—baseline opening

-K moves from stria vascularis to SM, into hair cells (through transduction current) and then out to perilymph (via K channels at the lateral wall of HCs), or supporting cells (via gap-junction) and then back to stria vascularis One direction in cycle

-This current w/o sound is called standing current

-Response to sound appear to be a modulation of standing current (either increase or decrease). But the direction nerve changes

Control of variable resistance (or the gating of MET): Tiplink Theory

-How deflecting stereocilia changes ion channel opening?

-It is controlled by the tip-side tip link

·The ion channels are located in the stereocilia

·The gates are at the attachment sites of tiplinks

Links across stereocilia

-Three types of links:

1) Row-to-row

2) Side-to-side

3) Tip-to-side (tiplink)

-1) and 2) are thicker, they hold the stereocilia together

-3) Control MET channels

Possible functions of the links

-Connect stereocilia together (the role of side-side, row-row links)

·Only the tallest stereocilia of OHCs contacts the TM

·Pathological evidence: disorganization of stereocilia by noise causes threshold shifting (damages hearing)

-Control of transduction ion channels: the role of tiplinks

Noise lesion to stereocilia

-Links among the cilia are the most fragile structure of the cochleae to noise

-Damage to the links causes the stereocilia to be disarranged, reduction of transduction efficacy is expected

Tip links are like spongy plugs

-Standing current: ion channels partially open (baseline opening) when quiet

-When the cilia bend laterally, the channel opening increases: depolarization

-Opposite, cilia bend medially, opening decreases: hyperpolarization

Transduction: cxcitation and suppression

-Bending laterally: more transduction channels are open, hair cells will be depolarized (by inward K current), IHCs release more neurotransmitters, auditory nerves are excited

·Ca channels (on the bottom of HC lateral wall) open

·[Ca] increases, resulting in

1. Ca-sensitive K+ channels at the lateral wall to open, and K+ out to perilymph—repolarization

2. Neurotransmitter release from HC

-Bending medially, transduction channel will be closed, the inward K current will be below that in standing current. HCs will be hyperpolarized (suppressed) because outward K current is the same. Auditory nerves are less excited

·Ca will be discharged

Three steps of signal processing in cochlea

1. Conduction: mechanical —> hydraulic mechanical —> macro —> micro mechanics

2. Transduction: mechanic —> electrical

·Bending of hair bundle

·MET channel open/close

·K inward and outward

·Ca inward —> two impacts: increased K outward, neurotransmitter release

3. Transmission: electrical (receptor potential)-biochemical (neurotransmitter release) —> action potential of SGN

OHCs versus IHCs

-IHCs are innervated by type I SGNs, OHCs by type II

-We know the function of only type I SGNs

-Therefore, IHCs are major groups sending information to central auditory system

-OHCs work as a mechanical amplifier (the intrinsic hearing aid)

How is IHC stimulated?

-More research is needed, but likely by hydraulic coupling

Normal (active) cochlea components

-Lower threshold (the lowest sound level to evoke response)

-Better frequency selectivity

The contribution of the active mechanism to hearing

-Improves sensitivity to sound (i.e., reduces threshold)

·Please note the terms: increased sensitivity means decreased threshold

·The gain change with intensity: high gain at low sound level—resulting compression

-Improves frequency selectivity

·Not sure what is the mechanism for this, OHC fast body motility is not frequency selective

·Likely related to hair bundle motility, but it is not clear if there is such motility in mammals

Evidence for OHC amplification

-Motility of OHCs (esp. fast body motility) in vitro was found to be in response to voltage change

-Lesion studies—OHC lesion —> poor tuning and poor sensitivity

-Otoacoustic emissions: ear can produce sound, this shows OHC function: generating mechanical force

Types of OHC motility

-Fast OHC body motility (main reason of amplification in mammals)

-Slow OHC body motility (not related to the amplification)

-Hair bundle motility—seen only in amphibians

·In mammals, there is only indirect evidence suggesting this mechanism (though likely responsible for frequency selectivity)

Fast OHC body motility

-Proportional to MP (membrane potential) changes

-Fast: flows up to 20 kHz

-Length change of up to 5%—1-5 micrometers, comparable to BM vibration by sound

-OHCs: depolarization causes hair cells to shorten, hyperpolarization causes hair cells to lengthen

Prestin

-As the OHC depolarizes, the length of the OHC becomes shorter

-The length change is voltage dependent, and mediated by the prestin (a membrane protein special for OHCs, the motor protein for OHC motility)

-Length change exerts impact on coupling to IHC from acoustic vibration