The function of cortical gain adaptation in detecting sounds in noise. Natural acoustic environments are highly variable; to function in them it is necessary to robustly represent important sounds despite changes in acoustic context. Recent studies have shown that neurons in primary auditory cortex (A1) modulate their response gain in an adaptive manner to account for changes in spectro-temporal statistics of different acoustic environments. Based on the results of studies across sensory modalities, we hypothesize that response gain is differentially modulated by two different types of cortical inhibitory neurons: parvalbumin-positive (PV) and somatostatin-positive (SOM) interneurons. Using this circuit-level mechanism, neurons can develop stimulus representations that are invariant to a variety of stimulus contexts by adaptively shifting their response gain. Here, we test whether and how gain adaptation shapes neural and behavioral responses to tones embedded in noise and examine how PV and SOM interneurons mediate this process. First, we examine how PVs and SOMs control gain adaptation by optogenetically manipulating these interneurons while recording neural responses in A1 to alternating low and high contrast noise bursts. We then measure and compute neural response gain at different temporal offsets relative to contrast transitions, and test how optogenetic manipulation of PV or SOM activity controls dynamic shifts in gain across multiple time scales. Next, we train mice to detect target tones at variable temporal delays relative to contrast transitions using a go-nogo paradigm while simultaneously recording neural activity and applying optogenetic inhibition of PVs and SOMs. With these data, we then test whether and how manipulations of neural gain impact neural coding and subsequent behavior. This research will, for the first time, examine the cell-specific cortical mechanisms underlying gain adaptation and their influence on behavioral detection of signals in noise, significantly improving our understanding of sound detection in variable acoustic environments.

Public Health Relevance

The goal of the proposed research is to test whether and how cortical gain adaptation affects behavioral detection of signals in noise. Identifying the neural correlates underlying signal in noise detection is a crucial step in understanding and developing treatments for patients suffering from hearing loss, whose ability to hear and communicate is disproportionately impaired in noisy environments. The proposed research will lead to new treatment approaches to vastly improve quality of life for these patients. Further understanding of the neural mechanisms that drive hearing in noise will lead to improved design and function of cochlear implants or hearing aids in the presence of noise.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DC016524-03
Application #
9764320
Study Section
Special Emphasis Panel (ZDC1)
Program Officer
Rivera-Rentas, Alberto L
Project Start
2017-09-01
Project End
2020-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Angeloni, C; Geffen, M N (2018) Contextual modulation of sound processing in the auditory cortex. Curr Opin Neurobiol 49:8-15