Hearing perception relies on our ability to tell apart the spectral content of different sounds, and to learn to use this difference to distinguish behaviorally relevant (such as dangerous and safe) sounds. The primary auditory cortex (A1) has been shown to play an important modulatory role in frequency discrimination and auditory discriminative emotional learning. However, despite decades of research that have carefully mapped the auditory response properties of neurons in A1, the neuronal circuits that underlie this modulation are currently unknown. The goal of the proposal is to test the role of such candidate neuronal circuit. In this proposal, we test the hypothesis that the activity of the most common class of interneurons, parvalbumin- positive (PVs), modulates selectivity to tones at different frequencies of excitatory neurons in A1, and that PV activity affects the behavioral performance in frequency discrimination and precision of discriminative auditory emotional learning. To measure the effect of PV activity we activate or inhibit PV interneurons selectively and temporally precisely using a recently developed optogenetic system, in awake behaving mice, and compare the neurometric and behavioral performance during activation or inactivation of PVs to baseline condition.

Public Health Relevance

This proposal will identify a cortical microcircuit, which facilitates auditory frequency discrimination and discriminative emotional learning. Understanding the function of ensembles of neurons in the central auditory system is crucial to understanding the neuropathology of hearing loss and tinnitus. If successful, our studies will lead to developing novel therapies for treatment of hearing and communicative disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC013660-02
Application #
8744274
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Platt, Christopher
Project Start
2013-09-27
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
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
Briguglio, John J; Aizenberg, Mark; Balasubramanian, Vijay et al. (2018) Cortical Neural Activity Predicts Sensory Acuity Under Optogenetic Manipulation. J Neurosci 38:2094-2105
Wood, Katherine C; Blackwell, Jennifer M; Geffen, Maria Neimark (2017) Cortical inhibitory interneurons control sensory processing. Curr Opin Neurobiol 46:200-207
Natan, Ryan G; Carruthers, Isaac M; Mwilambwe-Tshilobo, Laetitia et al. (2017) Gain Control in the Auditory Cortex Evoked by Changing Temporal Correlation of Sounds. Cereb Cortex 27:2385-2402
Blackwell, Jennifer M; Geffen, Maria N (2017) Progress and challenges for understanding the function of cortical microcircuits in auditory processing. Nat Commun 8:2165
Natan, Ryan G; Rao, Winnie; Geffen, Maria N (2017) Cortical Interneurons Differentially Shape Frequency Tuning following Adaptation. Cell Rep 21:878-890
Blackwell, Jennifer M; Taillefumier, Thibaud O; Natan, Ryan G et al. (2016) Stable encoding of sounds over a broad range of statistical parameters in the auditory cortex. Eur J Neurosci 43:751-64
Gervain, Judit; Werker, Janet F; Black, Alexis et al. (2016) The neural correlates of processing scale-invariant environmental sounds at birth. Neuroimage 133:144-150
Aizenberg, Mark; Mwilambwe-Tshilobo, Laetitia; Briguglio, John J et al. (2015) Bidirectional Regulation of Innate and Learned Behaviors That Rely on Frequency Discrimination by Cortical Inhibitory Neurons. PLoS Biol 13:e1002308
Mwilambwe-Tshilobo, Laetitia; Davis, Andrew J O; Aizenberg, Mark et al. (2015) Selective Impairment in Frequency Discrimination in a Mouse Model of Tinnitus. PLoS One 10:e0137749

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