Cortical assembly formation through excitatory/inhibitory circuit plasticity. Project Summary Throughout the brain, sensory information is thought to be represented by the joint activity of neurons that form functionally connected assemblies. A long-standing premise is that assemblies are formed during sensory learn- ing by strengthening the excitatory connections between co-active neurons. However, the role of inhibition in this process has yet to be fully elucidated. In this proposal, we will investigate the inhibitory and disinhibitory circuits that underlie the formation, stabilization and competition between neural assemblies. However, the con- tributions of specific interneuron classes to these processes is unknown. We have developed a theoretical model of assembly formation that incorporates data driven inhibitory synaptic plasticity rules for Parvalbumin (PV) and Somatostatin (SOM) expressing interneurons. Two key predictions arise from this model. First, PV interneu- rons provide inhibition that scales with excitation to stabilize neural assemblies. And second, SOM interneurons mediate competition between assemblies. In this proposal, we aim to experimentally test these predictions. In the olfactory cortex, we have found that odor discrimination training promotes assembly formation in response to rewarded odors but not unrewarded odors. In addition, we find that inhibition scales with excitation in the rewarded assembly. Thus, the olfactory cortex provides an ideal substrate to test predictions about the specific roles of PV and SOM neurons in assembly competition and stabilization. In Aim 1, we investigate the role of PV interneurons in maintaining excitation and inhibition balance and stabilizing rewarded assemblies. In Aim 2, we investigate the role for SOM interneurons in mediating inter-assembly competition. Finally, we have shown that a disinhibitory circuit mediated by vasoactive intestinal peptide (VIP) interneurons, gates recur- rent excitatory plasticity onto pyramidal neurons. This suggests an intriguing hypothesis that VIP interneurons inhibit SOM interneurons to promote the specific formation of the rewarded assembly. In Aim 3, we will use a combined theoretical and experimental approach to investigate the role of VIP-cell mediated disinhibition in gating assembly formation. The studies outlined in this proposal take a comprehensive approach to investigating the synaptic and circuit mechanisms that underlie assembly activity in the cortex. We focus on circuit motifs that are found in all cortices and we expect our findings will have broad impact across brain areas. Our findings will illuminate the important roles inhibitory and disinhibitory circuits play in assembly dynamics during sensory-guided behavior.

Project Narrative This study investigates the circuits and synaptic mechanisms that underlie the encoding of odor information by neural assemblies within the olfactory cortex. The main goal is to understand the relationships between changes synaptic strength, the formation and stabilization of neural assemblies, odor memories and ultimately learned behavior. These studies will provide insight to the circuitry of memory formation that may be compromised in neurodegenerative disorders.