Functional Organization of Primary Auditory Cortex

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Investigator: Christoph E. Schreiner, MD, PhD
Sponsor: NIH National Institute of Deafness and Communication Disorders

Location(s): United States

Description

Peripheral hearing loss has many consequences for the processing of sounds by the central nervous system such as the reduction of speech comprehension and, especially, understanding speech in background noise even for patients with only a mild cochlear hearing loss. We attempt to explore the normal function of the auditory cortex for processing complex signals and signals for different types of background noise in order to ascertain the mechanisms that lead to the normally very robust ability to process signals in noise. Once the normal functions are better understood, the detrimental consequences of hearing loss on these central mechanisms can be examined and may lead to the development of new therapeutic approaches to auditory communicative disorders.

 The long-term goal of the proposed experiments is to identify the fundamental processing principles and mechanisms that underlie auditory primary cortical receptive field generation and their processing of complex sounds. The principal hypotheses underlying the proposed work are that (i) neurons in primary auditory cortical fields express novel, emergent processing properties; (ii) multiple stimulus dimensions are expressed in each cortical neuron and govern nonlinear interactions that contribute to transformations toward a more robust, less variant sound representation; and (iii) these processing principles quickly adapt to changes in the stimulus statistics to enhance sound processing. The goal is to characterize these receptive field features, with extracellular and intracellular recordings and compare their properties across different cell types, cortical laminae and cortical fields to extrapolate their general properties and their potential contributions to human hearing. Optogenetic activity manipulation of inhibitory subsystems is utilized to better understand their role in cortical information processing. Aim 1 will assess multiple-feature receptive fields and their nonlinearities across input and output laminae of auditory cortical core areas in awake rats and mice, determine underlying synaptic contributions, and assess the role of parvalbumin- and somatostatin-positive interneurons in their formation. Aim 2 will determine how adaptation to stimulus statistics affects the receptive fields, their synaptic foundations, and the role of inhibitory subnetworks in this dynamic process. Combined these studies will establish a functional framework of signal processing in primary auditory cortical fields, reveal synaptic underpinnings, and explore the contributions of different inhibitory networks to shaping and adaption of cortical processing. Understanding these principles is crucial for a systematic evaluation of concurrent cortical processing principles, their role in normal auditory processing, in perceptual learning, and their potential contributions to auditory disorders.