Project Grant F31DC021883

SPATIOTEMPORAL MODELS OF NEURAL CODING IN THE VESTIBULAR PERIPHERY - PROJECT SUMMARY THE VESTIBULAR INNER EAR DETECTS HEAD MOTION THROUGH DISPLACEMENT OF MECHANOSENSITIVE STEREOCILIA BUNDLES ON HAIR CELLS (HCS). PRIMARY VESTIBULAR AFFERENTS ENCODE THESE BUNDLE DEFLECTIONS USING DISTINCT FIRING PATTERNS REFERRED TO AS REGULAR AND IRREGULAR BASED ON THE SPIKE TIMING VARIABILITY. BOTH AFFERENT CLASSES ENCODE HEAD MOTIONS USING SPIKE RATES BUT IRREGULAR AFFERENTS ALSO ENCODE FEATURES BASED ON PRECISE SPIKE TIMING. HC AND AFFERENTS ARE MODULATED BY EFFERENT VESTIBULAR NEURONS LOCATED IN THE BRAINSTEM. EFFERENTS LOWER HC VOLTAGE GAIN BUT EXCITE AFFERENTS AND THE LARGER IMPACTS OF EFFERENT FEEDBACK ON VESTIBULAR AFFERENT ENCODING AND VESTIBULAR- MEDIATED PERFORMANCE REMAIN HYPOTHETICAL. THREE KEY ASPECTS OF COMPUTATION IN THE VESTIBULAR PERIPHERY REMAIN TO BE INVESTIGATED. FIRST, VESTIBULAR AFFERENTS HAVE TYPICALLY MODELED SINGLE NEURONS TO EXPLAIN HOW A FEW BIOPHYSICAL PROPERTIES INFLUENCE NEURAL CODING. HOWEVER, THESE MODELS DO NOT CAPTURE THE ENTIRE PICTURE OF HOW THE VESTIBULAR PERIPHERY (I.E. THE POPULATION OF HCS AND AFFERENTS) ENCODES HEAD MOTIONS. SECOND, THE VESTIBULAR EPITHELIUM IS SPATIALLY ORGANIZED BY PREFERRED STIMULUS DIRECTION AND AFFERENT SUBTYPE - IRREGULAR AFFERENTS EMERGE FROM THE CENTRAL REGION OF THE EPITHELIUM (STRIOLA) WHILE REGULAR EMERGE FROM THE PERIPHERAL ZONE (EXTRASTRIOLA). THE ZONES SHOW DISTINCT PHYSIOLOGICAL AND STRUCTURAL PROPERTIES YET PRIOR MODELS HAVE ONLY INCORPORATED A FEW. IT REMAINS UNKNOWN HOW THESE VARIOUS PROPERTIES WORK TOGETHER AND CONTRIBUTE TO NEURAL CODING. FINALLY, PREVIOUS WORK HAS CHARACTERIZED HOW EFFERENTS MODULATE SPONTANEOUS HC AND AFFERENT DYNAMICS AT A SINGLE UNIT LEVEL, YET HOW THESE MODULATORY EFFECTS INFLUENCE MECHANICALLY EVOKED RESPONSES (I.E. HAIR BUNDLE DEFLECTIONS) AS WELL AS NEURAL CODING AT A POPULATION LEVEL IS UNKNOWN. THE OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP CIRCUIT-LEVEL COMPUTATIONAL MODELS OF THE VESTIBULAR PERIPHERY (I.E. A POPULATION OF HCS, AFFERENTS AND EFFERENT FEEDBACK) THAT INCORPORATES VOLTAGE-GATED ION CHANNELS, AFFERENT MORPHOLOGY, AND TOPOGRAPHICAL ORGANIZATION. THESE MODELS WILL GIVE US A HIGHER-LEVEL PERSPECTIVE ON HOW BIOLOGICAL PROPERTIES, SPATIAL ORGANIZATION AND EFFERENTS INFLUENCE BOTH NEURAL CODING AND RESPONSE DYNAMICS. OUR CIRCUIT-LEVEL MODELS MAY ALSO PROVIDE INSIGHT INTO VESTIBULAR EFFERENTS MODULATE AND STABILIZE VESTIBULAR FUNCTIONING.