Awarding the 1998 Nobel Prize in Medicine to researchers investigating nitric oxide (NO) in the periphery demonstrates the importance of NO as a modulator of nervous system function. However, the understanding of NO in the CNS has lagged behind the extensive progress in peripheral structures. The objectives of this research proposal are to increase our understanding of the dynamic roles NO plays in the CNS throughout the lifespan and to characterize NO release in the thalamus. The temporally distinct patterns of NOS expression in the thalamus make it an ideal model system to study retrograde and anterograde release. During development, NO may be important in guiding retinogeniculate axon termination. NO association with the parabrachial brainstem (PBR), a region involved in sleep/wake states, in the adult suggests it may be involved in modulating brain states, and may be a critical modulator of sensory information flow from the periphery to cortex.
The aims of this proposal are 1) to determine the source of NO in the developing LGN, 2) to determine if retinogeniculate stimulation causes NO release in the developing LGN and 3) to determine if activation of the PBR pathway results in NO release in the adult thalamus. Using the ferret LGN as a model, immunocytochemistry will be used to identify the neuronal elements expressing NOS in Aim 1 while a slice preparation will be used to investigate NO release in Aim 2. The cat LGN will serve as a model for complementary in vitro and in vivo approaches for Aim 3. Terminals will be activated pharmacologically and electrically, and the continuous rate and level of NO release will be determined. The mechanism of NO release will be verified through manipulation of the bNOS system The specific aims and experiments in this proposal are the cornerstone of my dissertation project. At the time of funding, I will have completed my preliminary exams and be ready to devote 100 percent effort to this research proposal.
