The function of the nervous system is dependent on complex interactions between networks of neurons. Understanding how these networks function in both health and disease is dependent on understanding the function of the fine-scale connections between neurons. The research proposed here is aimed at revealing the functions of specific connections between similar and different types of neurons in the same or different cortical layer. A rabies-based tracing system will reveal the direct monosynaptic connections between neurons in the primary visual cortex of mice. Visual stimulation combined with calcium imaging will then reveal the visual response properties of connected neurons. This method will be the first to simultaneously assess both connectivity and function in a live animal without limitations on the distance between connected cells. The cortical sources and functional contributions of excitatory and inhibitory inputs to single functionally characterized excitatory neurons will be uncovered, and the principles by which a single neuron integrates many inputs to produce a single functional output will be studied. The results of these experiments will shed light on various hypotheses about the functional roles of fine-scale connections in cortical information processing.
Understanding the function of detailed connections between neurons is necessary to obtain an adequate understanding of the function of neural networks in the cerebral cortex. Many diseases, such as Parkinson's disease, neuromuscular disorders, paralysis, schizophrenia, depression, autism, and attention disorders, are caused by dysfunction of precise neural networks. Understanding how these networks work is therefore likely to provide much insight into these diseases.
