The cerebral cortex is the dominant structural feature of the brains of humans and most other mammalian species. Its unique computational abilities are likely to underlie the emergence of many complex human skills, such as language and abstract reasoning, and the evolutionary success of mammals in general. Subtle differences in the organization or function of cortical circuits are therefore likely to underlie both the best and the worst of the human condition. Understanding how cortical circuits work is therefore key to revealing mechanisms that mediate brain dysfunction and strategies for their treatment. The studies proposed here are aimed at revealing the organization and function of neuronal connection in the cerebral cortex. The results are expected to provide insight into the computational strategies used for cortical information processing. Cortical circuits are composed of a complex network of many neuron types. Their function is dependent on how neurons are interconnected, how the connections function, and how the information delivered to individual neurons is integrated within the postsynaptic dendritic arbor. Despite extensive knowledge of the basic blueprint of cortical circuits, detailed knowledge about precisely which cell types are connected and how the multitude of connections onto a single neuron interact is limited. The studies proposed here will reveal the precise sources of functional excitatory and inhibitory input to single neurons in visual cortex. A novel laser scanning photostimulation method will be used to stimulate neurons that might make connections to a single neuron of interest, while recording electrical responses in that neuron to determine whether connections are present. With photostimulation it is possible to stimulate hundreds of sites to """"""""map"""""""" the sources of functional input to a single neuron. Results from these studies will reveal similarities and differences in the input to different types of inhibitory neurons and to inhibitory versus excitatory neurons. Interactions between excitatory and inhibitory inputs will be tested by combining photostimulation based mapping of input patterns with paired intracellular recordings from two neurons simultaneously. A single inhibitory neuron that is connected to an excitatory neuron of interest will be stimulated electrically during photostimulation mapping to determine whether the inhibitory input selectively disrupts excitatory input from different locations. These experiments are expected to provide insight into the basic mechanisms by which inhibitory and excitatory circuits interact to give rise to the complex function of dynamic cortical neural networks.
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