One of the long term interests of this laboratory has been the study of the relationship between cerebral blood flow and metabolism. There is evidence in the literature that nitric oxide is involved in both long-term potentiation and long- term depression and may also be involved in learning. These data all suggest a role for nitric oxide in activity dependent plasticity. This project will utilize a well characterized model of functional activation and plasticity to examine the role that nitric oxide plays in cerebral metabolic and flow plasticity and in the relationship between cerebral blood flow and metabolism. The model selected is the precisely organized rat facial vibrissa (whisker)-first somatosensory (S1) cortical """"""""barrel"""""""" sensory system. The precise organization of this system, coupled with the fact that the vibrissae are important tactile receptors in the rat's normal behavior, makes this an ideal system to investigate plasticity following either peripheral or central injury.
The specific aims of this project are to characterize the degree of functional reorganization of the adult somatosensory cortex following a peripheral lesion, and to determine the role of nitric oxide on this reorganization. Functional reorganization will be assessed with a double-label autoradiographic measurement of local cerebral glucose utilization (using [18F]fluorodeoxyglueose), and local cerebral blood flow (using [14C]iodoantipyrine), as well as with multiple site extracellular recordings of evoked multi-unit spike activity in S1 barrel cortex. Two preparations will be employed to examine plasticity in the somatosensory system. The first employs an unilateral deafferentation-spared vibrissa model in which all vibrissae, except one (#3 of row 6; SC3), are ablated in the adult rat followed two months later by measurements of local cerebral glucose utilization and local cerebral blood flow. In the intervening time, measurements of multi-unit activity will be made in the region of the S1 SC3. In these studies the nitric oxide/arginine system will be manipulated using inhibitors of nitric oxide synthase. This model provides data on the S1 cortical effect of a peripheral lesion. The second preparation employs adult bilateral SC3 deafferentation followed by training or conditioning of one SC3 vibrissa. These latter studies will be undertaken to characterize the metabolic SC3 reorganization of the S1 SC3 representation following unilateral SC3 conditioning, and to determine if changes in the conditioned metabolic representation will be abolished by chronic blockade of nitric oxide synthase. In addition to an examination of functional plasticity, this project will measure changes in the local nitric oxide concentration in the S1 vibrissa barrel bring vibrissa stimulation and will also utilize double label autoradiography to examine the role of nitric oxide in the, flow/metabolism couple. Investigation of the mechanism of functional plasticity, including the role of nitric oxide, provide important information regarding potential recovery of function after peripheral or central injury to the nervous system.
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