The function of the nervous system is dependent on complex interactions between networks of neurons composed of multiple neuron types. Understanding how these networks function both in health and disease is dependent on understanding the precise connectivity between specific neuron types and their functional interactions in the intact brain. It is therefore apparent that, in order to have an adequate understanding of the nervous system, it is necessary to have detailed descriptions of neuronal connectivity with the same level of precision at which these systems operate and to selectively manipulate and measure the activity of specific cell types in the context of the normal functioning network. The research proposed here is aimed first at revealing the detailed connectivity of inhibitory cortical neurons by developing and using a novel monosynaptic rabies circuit tracing strategy in which input neuron types are classified using single cell sequencing. The work will also develop and use a novel high throughput strategy for identification of cell type specific enhancer elements. The approach used will identify enhancers that can drive transgene expression in specific types of inhibitory cortical neurons. Together these studies will allow the development and testing of new hypotheses about the functional contributions of specific inhibitory cortical neuron types to perception,cognition and behavior.
Understanding the detailed organization of cortical circuits involving specific inhibitory neuron types is necessary to obtain a mechanistic understanding of the function of the cerebral cortex. Understanding the specific roles of inhibitory neurons in cortical function has important implications for human health, as these cell types and their activities are implicated in the cortical mechanisms that regulate attention and their disruption is implicated in schizophrenia and autism.
