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)
Type
Research Project (R01)
Project #
2R01DC008983-08A1
Application #
8762331
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Platt, Christopher
Project Start
Project End
Budget Start
Budget End
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
Li, Ling-yun; Ji, Xu-ying; Liang, Feixue et al. (2014) A feedforward inhibitory circuit mediates lateral refinement of sensory representation in upper layer 2/3 of mouse primary auditory cortex. J Neurosci 34:13670-83
Tao, Huizhong W; Li, Ya-tang; Zhang, Li I (2014) Formation of excitation-inhibition balance: inhibition listens and changes its tune. Trends Neurosci 37:528-30
Zhou, Mu; Liang, Feixue; Xiong, Xiaorui R et al. (2014) Scaling down of balanced excitation and inhibition by active behavioral states in auditory cortex. Nat Neurosci 17:841-50
Li, Ling-yun; Li, Ya-tang; Zhou, Mu et al. (2013) Intracortical multiplication of thalamocortical signals in mouse auditory cortex. Nat Neurosci 16:1179-81
Sun, Yujiao J; Kim, Young-Joo; Ibrahim, Leena A et al. (2013) Synaptic mechanisms underlying functional dichotomy between intrinsic-bursting and regular-spiking neurons in auditory cortical layer 5. J Neurosci 33:5326-39
Xiong, Xiaorui R; Liang, Feixue; Li, Haifu et al. (2013) Interaural level difference-dependent gain control and synaptic scaling underlying binaural computation. Neuron 79:738-53
Li, Ya-tang; Ibrahim, Leena A; Liu, Bao-hua et al. (2013) Linear transformation of thalamocortical input by intracortical excitation. Nat Neurosci 16:1324-30
Wang, Sheng-zhi; Ibrahim, Leena A; Kim, Young J et al. (2013) Slit/Robo signaling mediates spatial positioning of spiral ganglion neurons during development of cochlear innervation. J Neurosci 33:12242-54
Li, Ya-Tang; Ma, Wen-Pei; Pan, Chen-Jie et al. (2012) Broadening of cortical inhibition mediates developmental sharpening of orientation selectivity. J Neurosci 32:3981-91
Liu, Bao-hua; Li, Ya-tang; Ma, Wen-pei et al. (2011) Broad inhibition sharpens orientation selectivity by expanding input dynamic range in mouse simple cells. Neuron 71:542-54

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