From circuit motifs to computations: mapping the behavioral repertoire of cortical interneurons

Abstract

The exquisite architecture of cortex incorporates a myriad of inhibitory interneuron types. Until recently, the dearth of techniques for cell type identification in awake animals has made it difficult to link interneuron activity with circuit function, computation and behavior. This situation has changed dramatically in recent years with the advent of novel tools for targeting genetically distinct interneuron types so their activity can be observed and manipulated. The association of different interneuron subtypes with specific circuit functions, such as gain modulation or disinhibition, is starting to reveal canonical circuit motifs conserved across neocortical regions. Moreover, it appears that some interneuron types are recruited at specific behavioral events and likely control the flow of information among and within brain areas at behavioral time scales. Based on these results we propose that interneuron function goes beyond network coordination and interneurons should be viewed as integral elements of cortical computations serving behavior.

Figure 1. Network effects and behavioral correlates of identified interneuron classes

ab,c, Top, spike raster and peri-stimulus time histogram (PSTH) of Pv (a), Som (b) and Vip (c) interneurons aligned to light pulses. Bottom, PSTH of four simultaneously recorded unidentified neurons (Pv pairs, Som pairs and Vip pairs). Pv and Som pairs are inhibited after light pulses; Vip pairs are either inhibited (first and second PSTH) or show delayed activation (third and fourth PSTH), indicating disinhibition. d, Schematic depicting a mouse leaving the reward zone in a foraging task. e, Top two panels, spike raster and peri-event time histogram (PETH) of a Pv interneuron aligned to reward zone exit. Bottom, mean z-scored response of 14 PV neurons (shaded area indicates s.e.m.). f, Schematic depicting a mouse entering the reward zone in a foraging task. g, Top panels, spike raster and PETH of a NS-Som interneuron aligned to reward zone entry. Bottom, mean z-scored responses of 10 NS-Som neurons (shaded area indicates s.e.m.). h, Schematic of auditory go/no-go discrimination task. i, Top two panels, raster plots and PETHs of a Vip interneuron aligned to reinforcement (light green, reward; dark green, punishment; FA, false alarm). Bottom panel, mean z-scored responses of 10 Vip interneurons. Modified from refs and .

Figure 2. Disinhibitory microcircuit controlled by Vip interneurons

Vip interneurons receive long-range and local excitatory inputs as well serotonergic and cholinergic neuromodulatory projections from the dorsal raphe and nucleus basalis, respectively. They control the activity of a cortical pyramidal cell subpopulation by disinhibiting them mostly through Som interneurons.