Inhibitory microcircuits play an essential role in regulating cortical responses to sensory stimuli. Interneurons that inhibit dendritic or somatic integration act as gatekeepers for neural activity, synaptic plasticity, and the formation of sensory representations. Conversely, interneurons that selectively inhibit other interneurons can open gates through disinhibition. In the anterior piriform cortex, relief of inhibition permits associative LTP of excitatory synapses between pyramidal neurons. However, the interneurons and circuits mediating disinhibition have not been elucidated. In this study, we use an optogenetic approach in mice of both sexes to identify the inhibitory interneurons and disinhibitory circuits that regulate LTP. We focused on three prominent interneuron classes: somatostatin (SST), parvalbumin (PV), and vasoactive intestinal polypeptide (VIP) interneurons. We find that LTP is gated by the inactivation SST or PV interneurons and by the activation of VIP interneurons. Further, VIP interneurons strongly inhibit putative SST cells during LTP induction but only weakly inhibit PV interneurons. Together, these findings suggest that VIP interneurons mediate a disinhibitory circuit that gates synaptic plasticity during the formation of olfactory representations.

The inhibitory neuron population of the cortex can be subdivided into multiple cell classes with highly specialized local circuitry, gene expression, and response properties. PV and SOM neurons are two nonoverlapping cell classes with distinct but interacting functional roles, that depend on brain state. Here, we have applied a simple approach to identify PV, SOM, and putative pyramidal (Pyr) neurons within the same mice. We imaged their spike-related calcium activity in the posterior parietal cortex (PPC) while mice voluntarily ran on a spherical treadmill. We then related the activity of the simultaneously imaged neurons to each other, revealing that the activity of all inhibitory neurons was positively correlated compared to the activity within the Pyr population, and correlations were strongest among neurons of the same type. Furthermore, these activity relationships decayed with distance when comparing Pyr and inhibitory neurons, but not PV and SOM neurons. Finally, we identified coordinated activity events that were mostly restricted to either the PV or the SOM population, and used dimensionality reduction tools to reveal that these PV and SOM events were associated with different activity states in the Pyr population. This methodology will be useful to study population-level interactions across cell types in cortical circuits, and how they depend on behavioral state and task engagement.

Inhibitory microcircuits play an essential role in regulating cortical responses to sensory stimuli. Interneurons that inhibit dendritic or somatic integration in pyramidal neurons act as gatekeepers for neural activity, synaptic plasticity and the formation of sensory representations. Conversely, interneurons that specifically inhibit other interneurons can open gates through disinhibition. In the rodent piriform cortex, relief of dendritic inhibition permits long-term potentiation (LTP) of the recurrent synapses between pyramidal neurons (PNs) thought to underlie ensemble odor representations. We used an optogenetic approach to identify the inhibitory interneurons and disinhibitory circuits that regulate LTP. We focused on three prominent inhibitory neuron classes-somatostatin (SST), parvalbumin (PV), and vasoactive intestinal polypeptide (VIP) interneurons. We find that VIP interneurons inhibit SST interneurons and promote LTP through subthreshold dendritic disinhibition. Alternatively, suppression of PV-interneuron inhibition promotes LTP but requires suprathreshold spike activity. Thus, we have identified two disinhibitory mechanisms to regulate synaptic plasticity during olfactory processing.