1. 1. Auditory Physiology : Inner EarDr. Diptiman Baliarsingh1st Year PG, Dept. of ENT,Hi-Tech Medical College & Hospital,Bhubaneswar
2. 2. Introduction Snail-shaped osseous structure Coiled 2 & 2/3 turns around a central axis Modiolus With in the bony cochlea (osseous labyrinth) liesthe membranous labyrinth, consisting of Central scala media cochlear duct Superiorly, Scala vestibuli separated by Reissnersmembrane Inferiorly, Scala tympani separated by basilarmembrane The connection of scala vestibuli with the middleear occurs at Oval window, which is attached to
3. 3. Cross-section of Cochlea
4. 4. The Round window links the scala tympani tothe middle ear & is covered by Round windowmembrane The scala vestibuli & scala tympani merge at theapex of cochlea Helicotrema, & scala mediaends blindly S.V. & S.T. are filled with perilymph, extracellularfluid with High Na+ & Low K+ S.M. is filled with endolymph, composed of HighK+ & Low Na+ Cochlear Endolymph has electrical potential of+85mV This difference in ion composition and electricalpotential difference provide energy for cochleas
5. 5. Functional units of cochlea The Organ of Corti sensor of cochlea, converts &amplifies mechanical sound to electrical signals(Mechano-electrical Transduction) Stria Vascularis cochleas battery, generatesenergy (Endocochlear potential) The Spiral Ganglion these are neurons featuringaxons, electrical wires, transporting signals fromcochlea to CNS.
6. 6. The Organ of Corti & surr. structures
7. 7. THE ORGAN OF CORTI Named after Alfonso Giacomo Gaspare Corti It consists of two types of sensory receptors inner and outer hair cells There are about 3500 flask shaped Inner HairCells, lined up in a single row, through out entirelength of S.M. Lateral to IHCs lies 3 rows of Outer Hair Cells,cylindrical shaped. They contain hair bundles consists of Actin-filledstereocilia, graded acc. to height, with the mostlateral being the tallest and most medial rowbeing the shortest.
8. 8. The hair bundles of IHCs are organized as asmooth curved line of 2-3 rows of stereocilia &OHCs stereocilia bundles are arranged in ashallow V-shape. They are Mechano-sensitive organelles of H.C.s Every H.C. sits over a phalangeal supporting cell,i.e. Deiters Cells for OHCs The inner and outer pillar cells delienate the areabetween IHCs & OHCs framing the Tunnel ofCorti Other supporting cells embrace the hair cell-bearingpart of organ of corti
9. 9. Cochlear Stereocilia
10. 10. Medially, Inner Marginal Cells Laterally, Hensens (Outer Marginal) Cells Clauduis Cells Boettcher Cells The O.o.C. is covered by Tectorial membranealong its entire length, an acellular structure andis medially attached to spiral limbus & connectshair bundles to OHCs.
11. 11. The BASILAR MEMBRANE &TONOTOPY Sound eardrum vibration ear ossicles inner ear Movement of stapes causes displacement ofcochlear fluid in scala vestibuli The incompressibility of perilymph causes apressure gradient between SV & ST, leading tomovement of Basilar membrane & Organ of Corti Its like a TRAVELLING WAVE moving from baseto apex along the basilar memb.
12. 12. A pure tone stimulus, the travelling wave movesfrom base to apex, reaches a Maximum* at acharacteristic place along basilar memb. andthen decays This precise location of this Maximum dependson Frequency of stimulus the principle oftonotopic organisation of cochlea The base is tuned for frequencies of 20 kHz andapex for 20 Hz The tonotopic gradient is a continuous gradient inbasilar membrane width and also with changes inhair cell height and length of cellular structuresi.e. stereocilliary hair bundles
13. 13. Tonotopic organization of Organ of Corti
14. 14. Inner Hair Cells &Mechanoelectrical Transduction The IHCs are sensory cells which convertmechanical stimulation to electrical signals andthe synaptic activity is transmitted to brain This M-E Transduction occurs at tips ofstereocilia This apparatus is present in all hiar cells &consists of mechanically gated ion channels,that is closely asso. with elastic structures & aTip-link, that connects the tip of the stereociliumto the side of the next tallest stereocillium
15. 15. Components of Stereocilia Cadherin 23 & Protocadherin 15 components ofTip-Link Mechano-Electrical Transduction channel Insertional Plaque Myosin 1C Actin filaments Mechanical deflection of hair cell bundles leadsto mechanical tension leading to conformationalchange in transduction channel protein &increase in channel opening USHER SYNDROME - Congenital Hearing Loss+ Progressive loss of vision due to RetinitisPigmentosa
16. 16. On mechanical stimulation Towards the TALLEST row of stereocillia K+ &Ca++ ions enter hair cell through open M-E Tchannels, located near the tips leads toDEPOLARISATION of cell Towards the SHORTEST stereocillia, the M-E Tchannels close leads to HYPERPOLARISAITONof cell After a sustained excitatory deflection of hairbundle, the initial large transduction currentADAPTS, manifesting as decline of current correlated with closure of transduction channels 2 distinct process involved in adaptation1. Rapid reclosure of transduction channels2. Sliding of myosin based motor asso. withtransduction appa.
17. 17. Mechanoelectrical Transduction
18. 18. 1st - Rapid Channel reclosure Fast Adaptation Ca++ binding to intracellular site near ch. gate 2nd - Slow Adaptation 10 tmies slower than Fast Adap. Upper tip-link slides down the stereocilum During sustained stimulus, adaptation leads toresetting of restore point, hence allowing thetransduction apparatus to function at point ofhighest sensitivity The influx of Ca++ through open transductionchannels leads to slippage of myosin basedadaptation motor, which continuously strives tocrawl towards the stereocilliary tip along actincore
19. 19. The slippage of the myosin based motorchannels reduces the tension in the tip-linkcomplex & lowers the open probability of thetransduction channels, shutting off the Ca++influx At Low Ca++ levels myosins of the adaptationmotor will effectively move upwards readjusting the tension in the tip-link complex toa pointwhere the open probability ofthe M-E T ch. is close to theopen probability at rest. Myosin 1C is crucial for thisadaptation process
20. 20. OUTER HAIR CELLS & AMPLIFICATION OHCs have a key role in amplification of Basilarmemb. motion Amplification is necessary for detection of soundsat low pressure levels OHCs are mainly responsible forAMPLIFICATION & SHARP TUNING of Auditorysystem Mechanism of Amplification Somatic Electromotility the OHCs changetheir length by 3-5% in response to electricalstimulation
21. 21. When Depolarized, they Contract & whenHyperpolarized they Elongate The OHCs exert mechanical force causingmovements of basilar memb. motion caused by thetravelling wave Prestin motor protein responsible for somaticelectromotility in outer hair cells. It belongs to SLC26anion transporter superfamily mediateelectroneutral exchange of chloride & carbonateacross plasma membrane Hypothesis* - intracellular anions act as voltagesensors which bind to prestin and triggerconfirmational changes Hyperpolarisation anion binding to prestin increase in surface area of prestin cell elongation Depolarisation dissociation of anion decrease inthe prestin surf area cell contraction At rest anions are usually bound to prestin longer
22. 22. TECTORIAL MEMBRANE It is an extracellular structure overlying IHCs &OHCs & it changes its size from base to apex Only the tallest stereocillia of OHCs are directlyembeded into the undersurface of tectorialmembrane TM is attached on its inner edge to spiral limbus& is loosely connected to the supporting cells Hensens cells by trabeculae *Mutations in TM genes Alpha & Beta Tectorin caused profound hearing loss It is more like a resonant gel which is involved inenhancing the frequency selectivity of cochlea
23. 23. STRIA VASCULARIS Plays an important role in cochlear hemostasisby generating endocochlear potential &maintaining the unique ion compostion ofendolymph Highly vascularized, multi-layered tissue & is apart of lateral wall of SM 3 distinct cell types Marginal Intermediate Basal
24. 24. Stria Vascularis & K+ Circulation
25. 25. Tight junction demarcate strial tissue & provideionic barriers with marginal cells at one end &basal cells at other end The extracellular space between these twobarriers is known as intrastrial compartment Marginal cells separate endolymph filled scalamedia from interstitial compartment that is filledwith interstitial fluid Basal cells separate interstitial cells fromperilymph that surrounds fibrocytes of the spiralligament The intermediate cells as well as blood vesselsare embeded in intrastrial compartment
26. 26. Passage of ions from Perilymph to Endolymph in SV
27. 27. Gap junctions connect basal cells with withintermediate cells & with fibrocytes of spiralligament allowing Electric coupling &exchange of ions and small molecules The regulation of cochlear fluid homeostasisalso involves endolymphatic sac, whichresponds to endolymph volume disturbance Malfunctions in cochlear fluid homeostasis dueto disruptions of endocochlear potential, ioniccomposition, or its volume regulatingmechanism leads to varios forms of hearingimpariment
28. 28. ENDOCOCHLEAR POTENTIAL& POTASSIUM HOMEOSTASIS Hair cell mechanoelectrical transduction worksefficiently due to large driving force for cations toenter cells cytoplasm from scala media The +85 mV endocochlear potential ofendolymph & chemical gradient of K+ are themain components of the driving force HEARING THRESHOLD INCREASESAPPROXIMATELY BY 1dB PER 1mV LOSS OFENDOCOCHLEAR POTENTIAL
29. 29. K+ is the main cation of endolymph whichgenerates endocochlear potential Movement of K+ in cochlea 1. K+ can enter hair cells throughmechanoelectrical transduction channels & isreleased through hair cells basolateralmembranes into perilymphatic extracellularspace2. K+ can enter supporting cells and move towardsthe spiral ligament by extensive gap junctionnetwork3. Alternatively, K+ can diffuse extracellularly viaperilymphatic space Spiral ligament composed of Type II & Type Ifibrocytes take up K+ and provide anintracellular pathway into basal & intermediatecells of stria vascularis
30. 30. K+ flow through the Organ of Corti &Stria Vascularis
31. 31. K+ is released by intermediate cells via KCNJ10channels into interstitial space from which it isactively pumped & cotransported into marginalcells The marginal cells release K+ into SM The K+ circulation is NOT a TRUERECYCLING* Malfunctions of several K+ channels leads toperturbation of cochlear K+ homeostasis,resulting in hearing impairmentFor Ex loss of KCNE1 & KCNQ1 gene(encodes K+ ch subunits that allow secretion ofK+ from marginal cells to SM) leads to Jervelland Lange-Nielsen Syndrome chatz by HearingLoss & Cardiac Arrhythmia
32. 32. Passage of ions from Perilymph to Endolymph in SV
33. 33. The most well known genes involved in cochlearhomeostasis are the ones that encodeCONNEXIN Proteins Connexins form subunits of gap junctionchannels, which underlie K+ circulation networksdescribed for supporting supporting cells of theOrgan of Corti, the spiral ligament & striavascularis Mutations involving Connexins 26, 30, 31 & 43are responsible for majority of non-syndromichereditary hearing loss
34. 34. GENE PROTEIN PR. LOCATION PR. FUNCTION DISEASEKCNE1 KCNE1 Marginal Cells K+ Ch Jervell/Lange-Nielsen Synd.KCNQ1 KCNQ1 Marginal Cells K+ Ch Jervell/Lange-Nielsen Synd.KCNQ4 KCNQ4 OHCs & IHCs K+ Ch DFNA2GJB2 Cx26 Fibrocy. in SL & SLiEpi. on BM, I & B ClGap Junction Protein DFNB1/DFNA3GJB6 Cx30 Fibrocy. in SL & SLiSupp Cells of OoCGap Junction Protein DFNA3GJB3 Cx31 Fibrocy. in SL & SLiEpithelia on BMGap Junction Protein DFNA2, AR nonsynd. deafGJB1 Cx32 Fibrocy. in SL & SLiEpithelia on BMGap Junction Protein X-linked CharcotMarie-Tooth &DeafnessGJA1 Cx43 Fibrocy. in SL & SLiEpi. on BM, I & B ClGap Junction Protein AR nonsynd.deafnessBSND Barttin Marginal Cells Cl- Ch Ty 4 BarttersSyndrome
35. 35. COCHLEAR FLUIDHOMEOSTASIS Perilymph, Endolymph & Interstitial Fluid are 3types of fluids found in the cochlea & itsmetabolic support system The proper ionic composition of these fluids isessential for generation of endocochlear potential Perilymph & Interstitial fluid have High Na+ & LowK+ Endolymph have Low Na+ & High K+ , Low Ca++
36. 36. Ionic composition of Endolymph & PerilymphIons PERILYMPH ENDOLYMPHNa+ 148 1.3K+ 4.2 157Ca+ 1.3 0.023Cl- 119 132HCO3- 21 31pH 7.3 7.5
37. 37. In stria vascularis , influx of Na+ accompaniesK+ from the interstitial compartment intomarginal cells Cotransporter NKCC1 uses strong Na+ gradientto bring Na+, K+ & 2Cl- ions into marginal cells Na+/K+ ATPase sets up this gradient by bypumping Na+ into intrastrial space in exchangefor K+ Lastly, K+ leaves marginal cells to enterendolymphatic space This process maintains a High Na+ & Low K+concerntration of intrastrial fluid, which facilitatesK+ replenishment into intrastrial space
38. 38. Cl- is transported back to intrastrial space byCIC-K/Barttin Channels Inhibition of NKCC1 & Na+/K+ ATPase by LoopDiuretic Furosemide & Ouabain leads tosupression of E-C Potential Mut. of Barttin gene or Mut. of both CIC-Ka &CIC-Kb subunits of basolateral Cl- Ch. leads toBartters Synd Ty 4 chatz by Deafness & Renalsalt wasting Na+ is reabsorbed from endolymph by outersulcus & Reissners Memb cells, which play arole in maintaining Low Na+ conc of SM
39. 39. Ca++ regulation the tip-links break at very lowCa++ conc. & the mechanoelectical transductionchannels are blocked at high Ca++concerntrations Ca++ carries part of transduction current & playscritical roles in Adaptation & CochlearAmplification Ca++ permeable channels Ca++ ATPases &Na+/K+ exchangers are also found & regulateCa++ efflux & influx into Endolymph
40. 40. Cochlear Fluid VolumeRegulation It is equally important for cochlear funtion Previously, 2 popular theories Longitudinal &Radial Flow patterns1. Longitudinal Flow of endolymph is the secretionalong the membranous labyrinth withreabsorption in the endolymphatic duct & sac2. Radial Flow is based on local secretion &reabsorption, via stria vascularis Today, the prevailing thought is that there is nosignificant volume flow under physiologicalconditions
41. 41. A low volume flow inside the cochlea hasconsequences for intracochlear drug application,where under physiological conditions, diffusionof compounds inside the fluid filled compartmentappears to limit the equal dosing of potentialdrugs from base to apex At cellular level, transmembranous watermovement depends on aquaporins Aquaporin 2 found in Endolymph lining epitheliumof endolymphatic sac & is regulated byVasopressin Vasopressin also increases the activity ofepithelial Na+ ch & NKCC1 cotransporters foundin strial marginal cells & type II fibrocytes ofspiral ligament
42. 42. Glucocorticoids have opposite effects supresssymptoms of Menieres disease, by decreasingvasopressin production & altering expression ofcertain aquaporins Cochlear fluid homeostasis, Ion transport &Endocochlear potential are all req. for propercochlear function Ageing, affects long-term maintainance ofendocochlear potential & lowered metabolicrates of stria vascularis plays a role in age rel.hearing loss
43. 43. THE SPIRAL GANGLION Located in Rosenthals canal within the Modiolus ofthe cochlea It contains cell bodies of afferent neurons, itsdendrites are excited by neurotransmitter releasedby Organ of Corti, hair cells & the axons of whichare projects centrally into the cochlear nucleus, inbrain stem. Majority (95%) of afferent fibers are thick &myelinated, & originate from type I ganglionneurons, exclusively innervate IHCs Remaining (5%) of afferent fibers are thin,unmyelinated & originate from type II ganglionneurons, innervate OHCs
44. 44. Spiral ganglion innervations
45. 45. A dozen of type I ganglion neurons innervateeach IHCs Converging innervation pattern The type II afferent nerve fibers divide intomultiple branches & contact multiple OHCs Diverging innervation pattern All auditory information is carried to brainstemby afferent system, the auditory & vestibularnerves join each other forming vestibulocochlearnerve Efferent fibers originate in brain stem fromneurons located in Superior Olivary complex &send information to cochlea by synapsing withOHCs & with the afferent fibers beneath IHCs
46. 46. NEURAL PROCESSING OF AUDITORYINFORMATION & I.H.C. SYNAPSES Afferent NT release by IHCs is initiated at their 5-30ribbon type synapses, where local influx of Ca++through voltage gated Ca++ channels leads tofusion of synaptic vesicles at presynaptic sites Each ribbon synapse is composed of presynapticdense body & is surrounded by vesicles containingNTs, thick plasma memb, synaptic cleft & postsynaptic region containing AMPA-type glutaminergicreceptors of afferent nuerons
47. 47. The tonotopic organisation of the organ of cortiis also maintained within the afferent system,where the depolarisation of IHCs at specificlocation leads to excitation of connected afferentspiral ganglion neurons Each afferent is characterized by a specificturning curve, that decribes the sound pressurelevel of stimulus needed to elicit a response at agiven frequency The feature of turning curve is that they showthe frequency at which the nerve fibers displayshighest sensitivity its characteristic frequency Loss of cochlear amplification, i.e. by OHCsloss, leads to broadening of turning curve &increase in fibers response thresholds
48. 48. Tonotopic organisation of cochlea is the basisfor frequency coding in auditory nerve fibres Place Coding Frequency is coded by auditory nerve fibresdischarge characteristics Phase Locking, ithappens only at low frequencies Tonotopic organisation & Phase Locking areboth important for frequency discrimination Discharge rates are determined by frequency &intensity of stimulus
49. 49. As intensity increases, the discharge rate with ina single auditory nerve fibre increases, & the no.of auditory nerve fibers activated at a givencharacteristic frequency increases withintensifying stimuli The recruitment of more fibers is because ofauditory nerve fibers of same characteristicfrequency have different response thresholds With increased stimulus intensity, other afferentnerve fibres of nearby characteristic frequencyare also activated.
50. 50. EFFERNET INNERVATION OFCOCHLEA 2 different types of efferent fibers originate inbrain stem1. Myelinated Medial Olivocochlear (MOC)Efferents arise from neurons located aroundMedial Superior Olivary Nucleus. They project toC/L & I/L cochlea, where they form cholinergicsynapses with OHCs2. Unmyelinated Lateral Olivocochlear (LOC)Efferents arise from Lateral Superior OlivaryNucleus. Fibers project predominantly into I/Lcochlea, where they terminate on dendrites ofAfferent type I neurons beneath IHCs LOC efferent synapses are neurochemically
51. 51. The MOC system Stimulation of MOC system leads to increasedthresholds, due to decrease in the degree ofcochlear amplification by OHCs This sound-evoked feedback, decreasessensitivity of hearing apparatus whenmetabolically expensive amplifications systemsare not needed The LOC system Their direct input on afferent neurons, suggeststhey regulate afferent activity affects dynamicrange LOC feedback systems are slow & req. minutes tobecome effective It also additionally functions to perform slowintegration & adjustment of binaural inputs neededfor accurate binaural function & sound localization
52. 52. The activity of MOC & LOC efferent systemsseems to have protective effects againstacoustic injury, important in loud noiseenvironments.
53. 53. Thank You...REFERENCES Surgery of the Ear Glasscock-Shambaugh - 6thEd. Scott Browns Otorhinolaryngology & Head andNeck Surgery - 7th Ed. Cummings Otolaryngology & Head and NeckSurgery - 5th Ed. Mohan Bansal 2nd Ed.