An inhibitory pull–push circuit in frontal cortex

Abstract

Push-pull is a canonical computation of excitatory cortical circuits. Here we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP) expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feed-back pull-push influence on excitatory neurons – an inversion of the canonical push-pull of feed-forward input.

Target-specific co-transmission of acetylcholine and GABA from a subset of cortical VIP+ interneurons

“…The pattern of GABA connectivity we find, with VCIN GABAergic synapses onto a diversity of interneurons, especially superficial Sst + interneurons, is consistent with previous connectivity analysis of VIP interneurons (Karnani et al, 2016a;Pfeffer et al, 2013). This does not preclude further functional heterogeneity within VIP interneurons, as demonstrated by evidence that VIPs can directly inhibit excitatory pyramidal neurons (Garcia-Junco-Clemente et al, 2017;Zhou et al, 2017).…”

Amplifying the redistribution of somato-dendritic inhibition by the interplay of three interneuron types

“…The strength of this inhibition was highly variable between cells, covering a wide range of almost two orders of magnitude. Also, this connection was reported to be weaker in the occipital cortex in the same study (Garcia-Junco-Clemente et al, 2017). Notwithstanding the presence of this connection in different systems, it is tempting to speculate on its computational function, because it may enable to run different operating modes in parallel.…”

VPAC1 and VPAC2 receptor activation on GABA release from hippocampal nerve terminals involve several different signalling pathways

“…This, together with either paired recordings or channel rhodopsin‐assisted circuit mapping would be required to elucidate the dual effect of VIP on GABA release. This approach has been used recently to discriminate the role of different VIP‐expressing cortical interneurones in a push–pull inhibitory circuit (Garcia‐Junco‐Clemente et al ., ). A differential modulation of GABA release to interneurones and pyramidal cells by VIP is consistent with the current knowledge that GABAergic transmission to interneurones and to pyramidal cells is differently regulated (Jonas et al ., ) and with previous evidence (Cunha‐Reis et al ., , ) that VPAC 1 receptor activation is mainly associated with VIP modulation of synaptic transmission to pyramidal cell dendrites, whereas VPAC 2 receptor activation is preferentially associated with modulation of transmission to pyramidal cell bodies.…”