Cooperative Subnetworks of Molecularly Similar Interneurons in Mouse Neocortex

Abstract

Summary Simultaneous co-activation of neocortical neurons is likely critical for brain computations ranging from perception and motor control to memory and cognition. While co-activation of excitatory principal cells (PCs) during ongoing activity has been extensively studied, that of inhibitory interneurons (INs) has received little attention. Here we show in vivo and in vitro that members of two non-overlapping neocortical IN populations, expressing somatostatin (SOM) or vasoactive intestinal peptide (VIP), are active as populations rather than individually. We demonstrate a variety of synergistic mechanisms, involving population-specific local excitation, GABAergic disinhibition and excitation through electrical coupling, which likely underlie IN population co-activity. Firing of a few SOM or VIP INs recruits additional members within the cell type via GABAergic and cholinergic mechanisms, thereby amplifying the output of the population as a whole. Our data suggest that IN populations work as cooperative units, thus generating an amplifying nonlinearity in their circuit output.

Asymmetric effects of activating and inactivating cortical interneurons

“…Our inactivation experiments, on the other hand, mostly agree with (Lee et al, 2012), and support the idea that Pvalb+ cells subtractively suppress responses and increase information content by suppressing irrelevant spikes, whereas Sst+ cells divisively suppress responses to modulate dynamic range. However, we stress the caveat that both cell types may perform these operations in cooperation with other cell types (Karnani et al, 2016; Lee et al, 2013; Pfeffer et al, 2013; Pi et al, 2013; Xu et al, 2013) and through complex network dynamics that we have not identified here (Litwin-Kumar et al, 2016). Moreover, although it is often proposed that activation and inactivation of neuronal populations test their necessity and sufficiency, respectively, to support certain computations or drive specific behaviors, our results, along with previous work (rev.…”

Cell Type-Specific Gene Expression of Alpha 5 Subunit-Containing Gamma-Aminobutyric Acid Subtype A Receptors in Human and Mouse Frontal Cortex

“…One explanation for this result is that, since VIP cells are uniformly modulated by cholinergic and serotonergic transmissions via ionotropic receptors [40], VIP cell activation may be more likely to depend on cholinergic rather than GABAergic transmission. This was also demonstrated in an experiment showing that blockade of acetylcholine receptors attenuated VIP cell firing rate increases, whereas no such effect was found for GABA A R blockade [41]. Taken together, these studies suggest that neuromodulators such as acetylcholine, serotonin, and nicotinic agonists have crucial roles in driving the depolarization and recruitment of VIP cells and that the mechanisms underlying VIP cell regulation through GABAergic inhibition remain poorly understood.…”

GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits

“…For instance, as initial studies showed, PV-expressing FS cells within a distance of about 100–150 um are densely interconnected, as is the case among “LTS” SST-expressing INs, but FS cells and SST cells are not electrically connected to each other (Amitai et al, 2002; Galarreta and Hestrin, 1999; Gibson et al, 1999; Hestrin and Galarreta, 2005). Homotypic coupling has also been reported for multipolar bursting PV INs and irregular-spiking INs expressing cannabinoid receptors; presumably CCK basket cells (Blatow et al, 2003; Hestrin and Galarreta, 2005) as well as for VIP interneurons (Karnani et al, 2016). Electrical coupling between cells has therefore been interpreted as a strong indicator of INs belonging to the same subtype.…”