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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002260-25
Application #
9823870
Study Section
Auditory System Study Section (AUD)
Program Officer
Poremba, Amy
Project Start
1995-08-01
Project End
2020-11-30
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
25
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Pla, Ramon; Stanco, Amelia; Howard, MacKenzie A et al. (2018) Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis. Cereb Cortex 28:3797-3815
See, Jermyn Z; Atencio, Craig A; Sohal, Vikaas S et al. (2018) Coordinated neuronal ensembles in primary auditory cortical columns. Elife 7:
Malone, B J; Heiser, Marc A; Beitel, Ralph E et al. (2017) Background noise exerts diverse effects on the cortical encoding of foreground sounds. J Neurophysiol 118:1034-1054
Phillips, Elizabeth A K; Schreiner, Christoph E; Hasenstaub, Andrea R (2017) Diverse effects of stimulus history in waking mouse auditory cortex. J Neurophysiol 118:1376-1393
Vollmer, Maike; Beitel, Ralph E; Schreiner, Christoph E et al. (2017) Passive stimulation and behavioral training differentially transform temporal processing in the inferior colliculus and primary auditory cortex. J Neurophysiol 117:47-64
Cheung, Steven W; Atencio, Craig A; Levy, Eliott R J et al. (2017) Anisomorphic cortical reorganization in asymmetric sensorineural hearing loss. J Neurophysiol 118:932-948
Phillips, Elizabeth A K; Schreiner, Christoph E; Hasenstaub, Andrea R (2017) Cortical Interneurons Differentially Regulate the Effects of Acoustic Context. Cell Rep 20:771-778
Atencio, Craig A; Shen, Victor; Schreiner, Christoph E (2016) Synchrony, connectivity, and functional similarity in auditory midbrain local circuits. Neuroscience 335:30-53
Teschner, Magnus J; Seybold, Bryan A; Malone, Brian J et al. (2016) Effects of Signal-to-Noise Ratio on Auditory Cortical Frequency Processing. J Neurosci 36:2743-56
Atencio, C A; Schreiner, C E (2016) Functional congruity in local auditory cortical microcircuits. Neuroscience 316:402-19

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