Understanding the structure of cortical synaptic circuits is key to comprehending information representation and processing in the auditory cortex. However, due to technical limitations, the general structure of cortical synaptic circuits, and how this structure determines cortical function, remains largely unknown. As a first step to addressing this issue, in this project, we will investigate the patterns of excitatory and inhibitory synaptic inputs underlying the functional responses of individual cortical neurons and reveal the synaptic mechanisms determining or shaping these response properties. In the auditory cortex, patterns of synaptic inputs can be largely reflected by their frequency-intensity tonal receptive fields (TRFs). These patterns represent basic structural properties of synaptic input circuitry underlying the functioning of individual cortical neurons. Using an in vivo whole-cell recording technique, we will determine the "spectrotemporal" pattern of synaptic inputs for both excitatory and inhibitory neurons in the input layers of the adult rat auditory cortex. We will dissect the thalamocortical components of excitatory inputs by pharmacologically silencing the cortex. The cell type of recorded neurons will be determined by their spiking and morphological properties. We will determine excitatory and inhibitory synaptic mechanisms for the frequency/ intensity tuning of cortical pyramidal neurons by revealing the patterns of excitatory and inhibitory synaptic inputs with in vivo whole-cell voltage-clamp recording techniques. We will explicate the contribution of thalamocortical excitaotry inputs to the response properties of cortical neurons by developing a novel pharmacological approach to effectively and specifically silence the cortex. Finally, by distinguishing cortical inhibitory neurons according to histology and physiology, we will determine response properties of cortical GABAergic interneurons, and their underlying synaptic mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC008983-07
Application #
8518287
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
2007-08-01
Project End
2014-12-31
Budget Start
2013-08-01
Budget End
2014-12-31
Support Year
7
Fiscal Year
2013
Total Cost
$122,056
Indirect Cost
$47,175
Name
University of Southern California
Department
Physiology
Type
Schools of Medicine
DUNS #
072933393
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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