This proposal focuses on the development of somatosensory thalamocortical circuitry in mice with genetically impaired NMDAR function. 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. Mice with cortex-restricted disruption of NMDARs in excitatory neurons also display severe defects in cortical patterning within the somatosensory body map region. Thus, somatosensory region-specific knockout mouse models provide an excellent means to dissect out the role of NMDARs and downstream signaling molecules in patterning of pre- and postsynaptic neural elements. The long-term objective of this proposal is to reveal how somatosensory synaptic circuitry is altered following impaired NMDAR function. In vivo and in vitro electrophysiological approaches will be used to elucidate functional changes in the somatosensory cortex and thalamus of these mice. These studies will complement ongoing morphological analyses and overall reveal the role of NMDARs in organization and patterning of somatosensory neural maps.
NMDA receptors (NMDARs) play a major role in brain development, learning and memory, developmental neurological disorders, addiction, pain perception and in excitotoxicity. In this proposal we shall test the role of NMDARs in normal development of somatosensory neural circuits by examining physiological defects in region-specific genetic invalidation of NMDARs in mouse models. Understanding basic cellular and molecular mechanisms of NMDAR function in normal brain development is crucial for critical evaluation of developmental brain disorders and in developing therapeutic strategies.
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