Document text
Principal Investigator: Michele Insanally
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2024
Award: $489,915
Funding agency: National Institute on Deafness and Other Communication Disorders
Project Summary
Neurons throughout the auditory system are remarkably plastic, allowing auditory circuits to flexibly adapt to
changing task demands and context. Flexible auditory behavior is the result of a dynamic interaction between
several auditory regions including upstream and downstream areas. The auditory cortex (AC) is modulated by
many behavioral factors including expectation, enagagement, and reward supporting the view that it is a hub for
perception. However, AC does not operate in isolation receiving direct top-down inputs from frontal-motor cortex
(M2) and bottom-up inputs from auditory thalamus (MGB) forming a central auditory axis important for auditory
perception and behavior.
The canonical view of auditory circuits has exclusively focused on the role of classically responsive neurons.
Thus, non-classically responsive neurons with highly variable trial-to-trial firing patterns have typically been
excluded from analysis despite being widely reported for decades. Thus, the mechanisms by which non-classically responsive neurons contribute to auditory processing, perception, and behavior is unclear. The goal
of this proposal is to directly investigate how local circuits in AC comprised of diverse ensembles interact with
downstream and upstream auditory brain regions to flexibly gate auditory behavior. We will take an unbiased,
inclusive approach by considering the entire spectrum of classically to non-classically responsive neurons, to
auditory perception and learning. We will record spiking and synaptic responses from adult mouse AC (Aim1),
record simultaneously from AC and an auditory domain of frontal-motor cortex (M2; Aim 2), and record spiking
responses from auditory thalamus (vMGB; Aim 3) during learning and perform optogenetic experiments to reveal
synaptic mechanisms and network dynamics involved in perceptual learning. These experiments will provide
unique insight into the neural basis of flexible auditory behaviors, and help identity novel therapeutic targets for
improving hearing disorders.
Terms: <21+ years old><Acoustics><Adult><Adult Human><Animals><Area><Auditory><Auditory Cortex><Auditory Perception><Auditory area><Auditory system><Behavior><Behavioral><Brain><Brain Nervous System><Brain region><Cell Body><Cells><Central Auditory Processing Disorder><Communication><Computational toolkit><Cues><Development><Devices><Diagnosis><Dimensions><Disease><Disorder><Electrophysiology><Electrophysiology (science)><Encephalon><Environment><Exclusion><Frequencies><Goals><Hearing Disorders><Hearing Loss><Hearing problem><Hypoacuses><Hypoacusis><Injury><Language Development><Language Disorders><Learning><Learning Disorders><Measures><Mice><Mice Mammals><Motor Cortex><Murine><Mus><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Neurophysiology / Electrophysiology><Pathway interactions><Patients><Pattern><Perception><Perceptual learning><Phase><Physiologic><Physiological><Prevalence><Process><Property><Publishing><Reporting><Reversal Learning><Rewards><Role><Sensory><Shapes><Stimulus><Synapses><Synaptic><Synaptic plasticity><Task Performances><Techniques><Testing><Thalamic structure><Thalamus><Work><acquiring language skills><adulthood><auditory disease><auditory disorder><auditory dysfunction><auditory problem><auditory processing><auditory thalamus><computational toolbox><computational tools><computational toolset><computerized tools><deaf><deafened><density><developmental><developmental disease><developmental disorder><dysfunctional hearing><electrophysiological><expectation><experience><experiment><experimental research><experimental study><experiments><flexibility><flexible><hearing challenged><hearing defect><hearing deficient><hearing deficit><hearing difficulty><hearing disease><hearing dysfunction><hearing impairment><hearing perception><hearing restoration><improved><in vivo><injuries><insight><language acquisition><language deficit><language learning><learning outcome><neural><neural circuit><neural circuitry><neuro-prosthetic><neurocircuitry><neuronal><neuroprosthesis><neuroprosthetic><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><next generation><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><optogenetics><pathway><profound hearing loss><recruit><response><restore hearing><sensory gating><sensory input><social role><sound><sound perception><synapse><synaptic circuit><synaptic circuitry><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><thalamic>