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 #
5R01DC008983-12
Application #
9534584
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Poremba, Amy
Project Start
2007-08-01
Project End
2019-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
12
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Southern California
Department
Physiology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Zingg, Brian; Dong, Hong-Wei; Tao, Huizhong Whit et al. (2018) Input-output organization of the mouse claustrum. J Comp Neurol 526:2428-2443
Zhang, Guang-Wei; Sun, Wen-Jian; Zingg, Brian et al. (2018) A Non-canonical Reticular-Limbic Central Auditory Pathway via Medial Septum Contributes to Fear Conditioning. Neuron 97:406-417.e4
Zhang, Guang-Wei; Shen, Li; Zhong, Wen et al. (2018) Transforming Sensory Cues into Aversive Emotion via Septal-Habenular Pathway. Neuron 99:1016-1028.e5
Jing, Miao; Zhang, Peng; Wang, Guangfu et al. (2018) A genetically encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nat Biotechnol 36:726-737
Chou, Xiao-Lin; Wang, Xiyue; Zhang, Zheng-Gang et al. (2018) Inhibitory gain modulation of defense behaviors by zona incerta. Nat Commun 9:1151
Zingg, Brian; Chou, Xiao-Lin; Zhang, Zheng-Gang et al. (2017) AAV-Mediated Anterograde Transsynaptic Tagging: Mapping Corticocollicular Input-Defined Neural Pathways for Defense Behaviors. Neuron 93:33-47
Tao, Can; Zhang, Guangwei; Zhou, Chang et al. (2017) Diversity in Excitation-Inhibition Mismatch Underlies Local Functional Heterogeneity in the Rat Auditory Cortex. Cell Rep 19:521-531
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
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

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