Local Connections and In Vivo Physiology of Inhibitory Cortical Neurons

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DESCRIPTION (provided by applicant): Project Summary: Despite extensive knowledge of the basic blueprint of cortical circuits, detailed knowledge about the connectivity of specific cell types and how they function is still limited. The studies proposed here will investigate the laminar and fine-scale specificities of excitatory and inhibitory synaptic input to identified inhibitory neurons in the cerebral cortex, and will examine in vivo physiology of specific inhibitory cell types and their participation in regulating synchronous and oscillatory cortical activities. Recordings of specific inhibitory cell types can be facilitated by visualization of green fluorescent protein (GFP) expression restricted to known inhibitory neuron types in transgenic mice. Laminar specificity of functional input to specific cell types will be understood by using the technique combining whole cell recordings with scanning laser photostimulation. Furthermore, the fine-scale specificity of connections between pairs of neighboring inhibitory cells or excitatory and inhibitory cells will be revealed by cross-correlation analyses of synaptic responses evoked by photostimulation and recorded simultaneously from the neighboring pairs. In addition, to understand in vivo physiology and function of specific inhibitory cell types, targeted recordings under the guidance of 2- photon imaging will be made from these same cell types in GFP-expressing transgenic mice. We will record spikes from the target cells and measure local field potentials (LFPs) through electrocorticogram (ECoG) recordings. For each inhibitory neuron type, the overall spiking pattern in relation to LFPs and spike- triggered average of LFPs will be assessed to determine whether a correlative relationship exists between spike times and cortical oscillations. Other physiological properties of the recorded cells will also be assessed to further understand the properties of inhibitory neurons and their circuits. Relevance: Studies of the detailed organization of cortical circuits involving specific inhibitory cell types are necessary toward understanding cortical function. Understanding the specific roles of inhibitory cortical neurons has important implications for human health, as these cell types and their activities are involved in the cortical mechanisms that regulate attention and their disruption is implicated in schizophrenia.