Optical probing of inhibitory circuits in visual cortex

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The study of microcircuitry appears essential for the understanding the function of the nervous system. In the neocortex, the underlying microcircuitry remains largely unknown, due to the complexity of this structure and the technical challenges it creates. A major part of this complexity relates to the networks of inhibitory interneurons which appear extremely diverse in morphological and physiological properties, yet, arguably, could hold the key to cortical processing. The standard method to study synaptic connectivity of cortical neurons has been to perform dual recordings from closely neighboring pairs of neurons in slices in order to find connected pairs. Recently, Dr. Yuste's laboratory has developed an optical probing method that directly reveals excitatory synaptic circuits. This approach, however, relies on synaptic excitation and therefore cannot be applied to the study of inhibitory circuits. The goals of my proposal are to i) identify inhibitory circuits in mouse visual cortex using traditional dual recordings and ii) develop an optical probing method that reveals inhibitory synaptic targets. Specifically, I want to optically detect the neurons that are post-synaptic to two major types of interneurons (FS and LTS cells) n layer 5 mouse primary visual cortex. I will use two-photon imaging of post-synaptic [C1]-changes, low [CI]-ACSF experiments, image processing protocols under conditions where the activation of interneurons may silence post- synaptic targets and detection of correlated or anti-correlated spontaneous firing. The study of this microcircuitry can reveal the important role of these neurons in controlling critical periods for vision and related pathogenesis of ambiliopia.