Inhibitory Gating of Neural Circuits for Dynamic Representation of Distinct Odor Features

Sensory learning in the brain involves identifying the stimulus and associating it with a positive or negative value. It is generally believed that sensing and learning occur in separate brain areas: stable representation of sensory stimuli occurs in sensory cortices, while plastic learning occurs in a downstream region. Recent studies challenge this view by showing that odor features such as odor identity, concentration, and value are multiplexedly represented in the same brain region: the primary olfactory cortex. How are neurons and circuits wired up to mediate extraction of distinct odor features in the same brain region? In layer 2 of the anterior piriform cortex (APC), one of the largest regions of olfactory cortex, our group and others have recently identified two main principal neurons that differ in input as well as output connectivity patterns: semilunar (SL) and superficial pyramidal (SP) cells. It has been shown that SL cells are better activated by direct sensory inputs while SP cells are preferentially activated by associative inputs, hence SL and SP cells are parallel output channels that extract and represent different odor features. However, the neural mechanisms that gate the activation of SL vs. SP cells are unclear. Our preliminary data suggest that GABAergic interneurons differentially regulate SL vs. SP cells. Here, we propose that the plasticity and wiring of GABAergic interneurons providing inhibition to SL vs. SP cells are a key mechanism mediating this gating. This proposal is undertaken to examine the hypothesis that activity-dependent recruitment of inhibitory circuits differentially control SL vs. SP cell function, thereby dynamically regulating the output mode of APC. To probe the contribution of inhibitory synapses to SL vs. SP activity, I will use a combination of slice electrophysiology, optogenetics, sensory activity manipulation, mouse genetics, and immunofluorescent staining. Objective 1 will physiologically determine how excitatory and inhibitory circuits are differentially wired up for SL vs. SP cells. Objective 2 will examine how sensory experience modifies excitatory and inhibitory synapses of SL vs. SP cells. Objective 3 will examine whether parvalbumin-expressing inhibitory interneurons mediate the recurrent inhibition received by SL vs. SP cells. The synaptic and circuit mechanisms uncovered in this proposal will elucidate on how cortical circuits can selectively represent distinct sensory features and provide a framework for understanding how top-down projections or neuromodulators can influence these processes.