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.
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.
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