Somatosensory Cortical Development and Plasicity

Louisiana State Univ Hsc New Orleans, New Orleans LA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The role of neural activity in wiring and plasticity of sensory pathways is a major topic of interest in developmental neuroscience. During the past decade, considerable attention is directed toward the role of N-methyl D Aspartate (NMDA) receptor-mediated neural activity. A vast body of literature now underscores the importance of NMDARs during development of neural connections and their plasticity, learning and memory, as well as during excitotoxicity in pathological states of the mature nervous system. This supplemental proposal focuses on the development and plasticity of somatosensory thalamocortical circuitry in mice with cortex-specific null mutation of the essential subunit of the NMDAR, NRI. Rodent somatosensory pathway is an excellent model system to study development of topographic connections and patterning within somatosensory maps. Somatosensory patterns are abolished in the brainstem of mice lacking the critical subunit of the NMDARs. Mice that express lower levels of NMDAR function also show absence of patterning all along the somatosensory pathway. However, interpretation of results at the cortical level has been difficult, due to lack of region specificity in genetic manipulation of the NMDA receptor. We now have access to mice, which lack functional NMDARs in the neocortex, hippocampus and olfactory bulbs. These mice will undoubtedly allow us to dissociate cortical effects from subcortical ones. The long-term objective of this proposal is to reveal how axon arbors and dendritic processes of postsynaptic cells are altered following impaired NMDAR function. Combined molecular genetic and neuroanatomical approaches will be used to elucidate structural changes in the somatosensory cortex of these mice. A clear understanding of such anatomical changes will pave the way for dissecting out molecular mechanisms of pattern formation and plasticity in developing mammalian sensory pathways.