Nitric oxide-dependent synaptic plasticity in the retina

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This project addresses the role of nitric oxide in generating flexibility in neuronal communication in the central nervous system. Nitric oxide is a gaseous signaling molecule that is generated by the enzyme nitric oxide synthase in response to neuronal activity. Communication between neurons occurs at synapses and the activity of neurons and neuronal circuits are dependent upon the balance of excitatory and inhibitory synaptic interactions. Inhibition is dependent upon the concentration of chloride in the neuronal cytoplasm and it has been demonstrated that nitric oxide increases chloride concentration in the cytoplasm. Increasing cytosolic chloride has the effect of either reducing inhibition or converting it into excitation. Hence, nitric oxide can switch inhibition to excitation and alter the activity of neuronal circuits. This project will determine the sources of internal chloride that can be released by nitric oxide and the mechanisms involved in the release. The goals of the project will be achieved using a combination of electrophysiology and molecular biology. This work is fundamental to our understanding of nervous system function because control of cytosolic chloride by nitric oxide is a previously undiscovered mechanism that dramatically increases the flexibility of normally inhibitory synapses. Furthermore, the project explores the nitric oxide release of internal chloride in a retinal neuron but this chloride release has also been demonstrated in neurons from elsewhere in the brain. As such, these results will have important ramifications for regulation of synaptic function in multiple regions of the central nervous system. The broader impacts include participation by graduate students and undergraduates in the PI's laboratory. The PI will participate in the College of Science Louisiana Biomedical Research Network Summer Research Program, and the LSU Howard Hughes Medical Institute Undergraduate Summer Research Program. In these programs, the PI will recruit underrepresented minorities and women. In addition, the PI is a mentor at the Louisiana Math and Science Teacher Institute, which provides additional science education for local public school teachers.