CaMKII, MAPK, and CREB are coactivated in identified neurons in a neocortical circuit required for performing visual shape discriminations.

Current theories postulate that the essential information for specific cognitive tasks is widely dispersed in multiple forebrain areas. Nonetheless, synaptic plasticity and neural network theories hypothesize that activation of specific signaling pathways, in specific neurons, modifies synaptic strengths, thereby encoding essential information for performance in localized circuits. Consistent with these latter theories, we have shown that gene transfer of a constitutively active protein kinase C into several hundred glutamatergic and GABAergic neurons in rat postrhinal cortex enhances choice accuracy in visual shape discriminations, and the genetically-modified circuit encodes some of the essential information for performance. However, little is known about the role of specific signaling pathways required for learning, in specific neurons within a critical circuit. Here we show that three learning-associated signaling pathways are coactivated in the transduced neurons during both learning and performance. After gene transfer, but before learning a new discrimination, the calcium/calmodulin-dependent protein kinase (CaMKII), MAP kinase, and CREB pathways were inactive. During learning, these three pathways were coactivated in the transduced neurons. During later performance of the discrimination, CaMKII activity declined, but MAP kinase and CREB activity persisted. Because the transduced neurons are part of a circuit that encodes essential information for performance, activation of these learning-associated signaling pathways, in these identified neurons, is likely important for both learning and performance.