During development, sensory experiences produce synaptic modifications that specify the capabilities and limitations of brain function in adults. In adults, very similar modifications appear to be the substrates of learning and memory. Therefore, a question of great significance is how synapses in the brain are modified by sensory experience. Mechanisms for long-term synaptic depression (LTD) and potentiation (LTP) have been identified, as has a mechanism for regulating the conditions for LTP induction. However, it remains to be determined the extent to which these mechanisms contribute to naturally occurring modifications in the brain. The mouse visual cortex provides an excellent model system for addressing this question. Visual cortex is well-known to be modified by simple manipulations of experience, such as depriving one eye of vision, and the mouse can be genetically modified to test specific hypotheses about molecular mechanisms. Moreover, while this type of plasticity changes over the course of postnatal life, it persists in adult mouse visual cortex and therefore can provide insight into how age alters the qualities of synaptic plasticity in the cerebral cortex.
The aims of this proposal are to determine (1) the qualities of visual cortical plasticity across the life-span, (2) the contributions of LTD mechanisms to deprivation-induced response depression in vivo, (3) the contribution of LTP mechanisms to experience-dependent response potentiation in vivo, and (4) if changes in NMDA receptor subunit composition are permissive for experience-dependent response potentiation in vivo.
These aims will be accomplished by taking advantage of the special expertise of this Center in mouse genetics, chronic recording, and the molecular bases for synaptic plasticity.
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