Neocortical SHANK1 regulation of forebrain dependent associative learning.

Learning-induced neocortical synaptic plasticity is a well-established mechanism mediating memory consolidation. Classic learning paradigms elicit synaptic changes in various brain regions including the neocortex. Work from our laboratory has further suggested synaptic remodeling in primary somatosensory cortex (S1) during forebrain-dependent associative learning. While this process of synaptic remodeling is largely believed to contribute to memory consolidation, the underlying processes mediating this plasticity are poorly understood. Interestingly, abnormal expression of the synaptic scaffolding protein SHANK1 has been linked with aberrant synaptic plasticity and learning impairments, suggesting that it plays a critical role in these processes. However, a direct analysis of the role for SHANK1 during learning in the neocortex, the most likely site for memory storage, has never been adequately explored. To directly examine SHANK1's potential role during learning and memory, the following study set out to both examine neocortical SHANK1 expression during a learning event and determine the consequences of reducing neocortical SHANK1 expression on learning. The current study found that SHANK1 expression is transiently increased during periods of learning-induced dendritic spine plasticity in the neocortex. Furthermore, shRNA-mediated neocortical SHANK1 knockdown significantly impairs acquisition for the forebrain-dependent associative learning task (whisker-trace-eyeblink conditioning). Consistent with these findings, SHANK1 has been implicated in various neurological disorders. Collectively, these findings suggest a role for SHANK1 in neocortical learning-induced dendritic spine plasticity underlying learning and normal cognition; thus, providing potential insight into neurological mechanisms mediating abnormalities of impaired cognition.