Inhibitory Cell Types, Circuits and Receptive Fields in Mouse Visual Cortex

The diversity and the specialized connectivity and function of inhibitory cortical neurons have been the focus of intense research for many decades (Fishell and Rudy, Ann Rev Neurosci 34:535–567, 2011). Until recently, technical limitations have restricted the power of experiments that could be conducted in vivo. Nevertheless, in vitro studies identified dozens of distinct cortical inhibitory neuron types, each with unique chemical properties, intrinsic firing properties and connection specificity. And at the same time, post-mortem studies from human patients have demonstrated defects of inhibitory circuit markers in diseases such as schizophrenia (Curley and Lewis, J Physiol 590:715–724, 2012; Stan and Lewis, Curr Pharm Biotech 13:1557–1562, 2012; Lewis, Curr Opin Neurobiol 26:22–26, 2014). Together, these observations have led to the hypothesis that distinct types of inhibitory neurons play distinct functional roles in the dynamic regulation of brain states and in the context-dependent extraction of sensory information, cognitive function, and behavioral output—functions thought to be disrupted in disorders such as schizophrenia and autism. Despite the wealth of evidence in support of this hypothesis, tools have only recently emerged to allow detailed studies of neural circuit mechanisms underlying in vivo dynamics and to implicate specific inhibitory cell types and connections in specific functions (Luo et al., Neuron 57:634–660, 2008). Now, rather than broadly surveying inhibitory neuron properties and connections in vitro, studies have begun to focus more deeply on the in vivo contributions of those inhibitory cell types that are genetically accessible and can therefore be interrogated with modern genetic tools for manipulating and monitoring activity of specific cell types. Mouse lines that express Cre-recombinase selectively in three major, non-overlapping groups of inhibitory cortical neurons—Parvalbumin-expressing (PV), somatostatin-expressing (SST), and vasoactive intestinal peptide-expressing (VIP; Lee et al., J Neurosci 30:16796–16808, 2010; Xu et al. J Comp Neurol 518:389–404, 2010; Rudy et al., J Comp Neurol 518:389–404, 2011; Taniguchi et al., J Comp Neurol 518:389–404, 2011)—have allowed detailed studies of the connectivity and in vivo functional roles of these cell groups. Such studies have implicated PV inhibitory neurons in gain control (Atallah et al., Neuron 73:159–170, 2012; Lee et al., Nature 488:379–383, 2012; Nienborg et al., J Neurosci 33:11145–11154, 2013), SST interneurons in the suppression of lateral and feedback (top-down) interactions (Adesnik and Scanziani, Nature 464:1155–1160, 2010; Nienborg et al., J Neurosci 33:11145–11154, 2013), and VIP interneurons in the dynamic regulation of SST cells under the control of brain state-dependent neuromodulators (Kawaguchi, J Neurophysiol 78:1743–1747, 1997; Alitto and Dan, Front Syst Neurosci 6:79, 2012; Lee et al., Nat Neurosci 16:1662–1670, 2013; Pi et al., Nature 503:521–524, 2013; Polack et al., Nat Neurosci 16:1331–1339, 2013; Fu et al., Cell 156:1139–1152, 2014; Stryker, Cold Spring Harbor Symp Quant Biol 79:1–9, 2014; Zhang et al., Science 345:660–665, 2014).