Why have a coiled cochlea? “The spiral acts like a whispering gallery and redistributions the wave energy to increase the pressure difference across the cochlear partition in the radial direction, away from the modiolus. This has a tendency to increase the motion of the reticular lamina toward the modiolus, for a given upward motion of the basilar membrane, which in turn tends to shear the hair cell bundles more in the depolarizing direction. The effect is greatest at the apex where low frequencies are processed. The greater the ratio of the radius of curvature of the basal turn to that of the apical turn, lowers the low frequency limit of any mammal we have looked at, from mouse to whale. All the best, Richard” (Richard Chadwick, NIH, NIDCD Section on BioPhysics) -increases low frequency signal by dB with ratio >8 (h=10)

502 Lecture #2: The cochlea, place coding, active process

Cochlear cross-section at a single turn

The organ of Corti

Mid-basal turn guinea pig O.Corti * Tunnel of Corti efferent fibersOHC bodies 20 u

Tho stiff, longer stereocilia are more flexible. While not proven, longer stereocilia and a wider basilar membrane may aid in low frequency detection.

Tonotopic organization

von Bekesy’s experiments (1950s) Using cadavers (human and animal) Temporal bone was rapidly dissected In saline rubber replaced oval/round windows Mechanical vibrator replaced stirrup Cochlear wall opened, exposing Reissner’s mbr Silver particles on mbr visualized with scope / strobe Two types of experiments: –Opened length of cochlea, plotted waveforms and envelopes for sounds of different frequencies –Opened cochlea at certain points, measured vibrations at those points with different frequencies

Base Apex Low High FREQUENCY PLACE BASILAR MEMBRANE DISPLACEMENT Exposed cochlear partition; stimulation with one frequency

Base Apex Low High FREQUENCY PLACE BASILAR MEMBRANE DISPLACEMENT

Apex Wider basilar mbr Low frequency

Each curve represents the reponses von Bekesy observed when he studied the reponses of one place along the cochlea to stimulation with a range of frequencies with loud tones. From von Bekesy, 1960 Distance from stapes 24 mm

Frequency place code!

von Bekesy’s findings Insights: –Sound vibration gives traveling wave with gradual rise and rapid fall off –Cochlea has frequency-specific place code Limitations: –Used non-physiological amplitude Needed 130 dB to see Ag + particles move –Measurements made on cadavers Normal responses require live animal –The active process Nobel prize in Medicine, 1961

Low High FREQUENCY Base Apex PLACE BASILAR MEMBRANE DISPLACEMENT INTENSITY Bekesy Stimulus LINEAR

Low High FREQUENCY Base Apex PLACE BASILAR MEMBRANE DISPLACEMENT INTENSITY NONLINEAR Cochlear Amplifier

Displacement as a function of frequency Parameter: sound intensity Threshold as a function Of sound intensity From Sellick, ea 1982

Low High FREQUENCY Base Apex PLACE BASILAR MEMBRANE DISPLACEMENT INTENSITY NONLINEAR Cochlear Amplifier Threshold level

Characteristics of the Active Process Is frequency specific, following place code of the cochlea –All cellular machinery aligned at frequency Requires metabolic energy –Not present in dead cochlea Depends on the endolymphatic cochlear battery –Furosemide decreases [K + ], stops process

Principal Receptor Sends frequency-specific Information to brain based on the vibratory pattern of the basilar membrane Receptor/Effector (cochlear amplifier) Provides frequency-specific energy to the basilar membrane. Compressive nonlinearity - enhance responses to low level stimuli. Powered by endocochlear potential. Compare:

Afferent Efferent Cochlear nerve axons How can we measure the energy of the cochlear amplifier?

Distortion Product Otoacoustic Emissions (DPOAEs) dB SPL 50 0 f1f1 f2f Primary Tones 2f 1 -f 2 Emission generated by OHCs through an active process S. Blatrix & R. Pujol.

Receptor/Effector (cochlear amplifier) Provides frequency-specific energy to the basilar membrane. Compressive nonlinearity - enhance responses to low level stimuli. Powered by endocochlear potential. The outer hair cell motor protein: Prestin - isolated One member of a large class of sugar transporters. Co-opted to be a motor protein. Localized to basolateral membrane. Voltage sensitive. From Adler, ea. Hearing Res. 184:27, 2003

Cloned prestin gives motility to tsa cells a) Transfected cell sucked into pipet b) Response to 200Hz stim by 2 prestin cells (top); control c) Reduced by salicylate (comp at anion site) d) Responses to 200Hz and 1kHz commands e) Fourier transform of responses in d.

Prestin KO mice Electromotility is lost in -/- mice ABRs, DPOAEs are lost in -/- mice From Liberman, etal. Nature 419:300, 2002

Summary - Cochlea Traveling waves distribute frequency specific excitation along cochlear epithelia Outer hair cells amplify displacement of basilar membrane - the cochlear amplifier! Inner hair cells transform frequency specific mechanical activity into electrical activity - auditory encoding based on a place code! Molecular components are being defined largely through study of deafness genes