Inhibitory synaptic circuits play important roles in shaping cortical processing. Our understanding of the functional engagement of inhibitory circuits composed of different inhibitory cell types however remains poor. The recent development of molecular and genetic tools in the mouse, in combination with the innovative techniques of in vivo electrophysiology, has now made it possible to systematically dissect synaptic circuitry underlying specific cortical functions. In this project, we will integrate multile approaches to investigate the synaptic, in particular inhibitory circuitry mechanisms underlying auditory processing in the mouse primary auditory cortex (A1). In the first part, we will apply in vivo cell-attached and whole-cell recordings to investigate synaptic mechanisms for specific laminar processing in A1, a direct extension of the previously funded project. Second, we will combine in vivo two-photon imaging and patch-clamp recordings and utilize optogenetic methods to dissect functional roles of different types of inhibitory neuron. Finally, with high-quality whole-cell recordings in awake behaving mice, we will investigate cortical synaptic circuitry mechanisms for auditory processing functions in awake cortex, and their modulation by different behavioral states.

Public Health Relevance

Understanding the organization of synaptic circuits that determines the normal functional properties of individual cortical neurons is necessary for identifying circuit components that may go awry in psychiatric and neurological disorders. In this project, we propose to unravel the excitatory and inhibitory synaptic circuitry mechanisms for fundamental auditory processing functions in the mouse primary auditory cortex by integrating several innovative approaches. The proposed studies will generate new insights for our understanding of the physiology and pathology of the auditory cortex, in particular of how changes in the cortical inhibitory circuits, as implicated in several neurological diseases, can lead to abnormal perceptual functions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC008983-08A1
Application #
8762331
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Platt, Christopher
Project Start
2007-08-01
Project End
2019-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Southern California
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Ji, Xu-Ying; Zingg, Brian; Mesik, Lukas et al. (2016) Thalamocortical Innervation Pattern in Mouse Auditory and Visual Cortex: Laminar and Cell-Type Specificity. Cereb Cortex 26:2612-25
Kim, Young J; Ibrahim, Leena A; Wang, Sheng-Zhi et al. (2016) EphA7 regulates spiral ganglion innervation of cochlear hair cells. Dev Neurobiol 76:452-69
Ibrahim, Leena A; Mesik, Lukas; Ji, Xu-Ying et al. (2016) Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition. Neuron 89:1031-45
Kim, Young J; Wang, Sheng-zhi; Tymanskyj, Stephen et al. (2016) Dcc Mediates Functional Assembly of Peripheral Auditory Circuits. Sci Rep 6:23799
Tao, Can; Zhang, Guangwei; Zhou, Chang et al. (2016) Synaptic Basis for the Generation of Response Variation in Auditory Cortex. Sci Rep 6:31024
Li, Ling-Yun; Xiong, Xiaorui R; Ibrahim, Leena A et al. (2015) Differential Receptive Field Properties of Parvalbumin and Somatostatin Inhibitory Neurons in Mouse Auditory Cortex. Cereb Cortex 25:1782-91
Albers, Mark W; Gilmore, Grover C; Kaye, Jeffrey et al. (2015) At the interface of sensory and motor dysfunctions and Alzheimer's disease. Alzheimers Dement 11:70-98
Liang, Feixue; Xiong, Xiaorui R; Zingg, Brian et al. (2015) Sensory Cortical Control of a Visually Induced Arrest Behavior via Corticotectal Projections. Neuron 86:755-67
Zhou, Mu; Li, Ya-Tang; Yuan, Wei et al. (2015) Synaptic mechanisms for generating temporal diversity of auditory representation in the dorsal cochlear nucleus. J Neurophysiol 113:1358-68
Mesik, Lukas; Ma, Wen-pei; Li, Ling-yun et al. (2015) Functional response properties of VIP-expressing inhibitory neurons in mouse visual and auditory cortex. Front Neural Circuits 9:22

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