Hearing loss affects synaptic balance in auditory cortex

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DESCRIPTION (provided by applicant): Hearing loss can perturb speech and language acquisition and ultimately compromise cognitive performance. The core hypothesis of this proposal is that sensorineural (SNHL) or conductive hearing loss (CHL) disrupts the balance between excitatory and inhibitory conductances, and severely limits the ability of primary auditory (Al) cortex neurons to encode acoustic cues. Deafness will be surgically induced before hearing onset in gerbils, and the properties of Al pyramidal neurons will be examined using whole-cell recording techniques in a thalamocortical brain slice preparation. The research plan will address four major issues: (1) Does hearing loss influence intrinsic properties in Al? Changes in Al neuron electrical characteristics will be examined, including electrotonic and firing properties, and key inward and outward currents. (2) Does hearing loss influence excitatory synapses in Al? Changes in thalamus-evoked excitatory postsynaptic currents (EPSCs) will be investigated, including their amplitude and kinetics. Pre-or postsynaptic involvement will be assessed with focal delivery of agonists, mEPSC analyses, and EPSC failure rates. (3) Does hearing loss influence inhibitory synapses in Al? Changes in intracortically evoked inhibitory postsynaptic potentials (IPSPs) will be studied, including the pharmacology of GABAa and GABAb receptor mediated components. Pre-or postsynaptic involvement will be assessed with focal delivery of GABA agonists, and miniature IPSCs. (4) Does hearing loss affect cortical processing? Changes in temporal processing will be explored by stimulating thalamic afferents with trains of rectangular or sinusoidal current pulses while recording EPSPs in Al. Synaptic integration will be assessed by timing intracortical inhibition with current- or thalamus- evoked action potentials. Together, the results are significant for understanding at a cellular level how auditory processing is influenced by mild to severe deafness, and how we might compensate for these deficits.