VIP-Expressing GABAergic Neurons: Disinhibitory vs. Inhibitory Motif and Its Role in Communication Across Neocortical Areas

Abstract

GABAergic neurons play a crucial role in shaping cortical activity. Even though GABAergic neurons constitute a small fraction of cortical neurons, their peculiar morphology and functional properties make them an intriguing and challenging task to study. Here, we review the basic anatomical features, the circuit properties, and the possible role in the relevant behavioral task of a subclass of GABAergic neurons that express vasoactive intestinal polypeptide (VIP). These studies were performed using transgenic mice in which the VIP-expressing neurons can be recognized using fluorescent proteins and optogenetic manipulation to control (or regulate) their electrical activity. Cortical VIP-expressing neurons are more abundant in superficial cortical layers than other cortical layers, where they are mainly studied. Optogenetic and paired recordings performed in ex vivo cortical preparations show that VIP-expressing neurons mainly exert their inhibitory effect onto somatostatin-expressing (SOM) inhibitory neurons, leading to a disinhibitory effect onto excitatory pyramidal neurons. However, this subclass of GABAergic neurons also releases neurotransmitters onto other GABAergic and non-GABAergic neurons, suggesting other possible circuit roles than a disinhibitory effect. The heterogeneity of VIP-expressing neurons also suggests their involvement and recruitment during different functions via the inhibition/disinhibition of GABAergic and non-GABAergic neurons locally and distally, depending on the specific local circuit in which they are embedded, with potential effects on the behavioral states of the animal. Although VIP-expressing neurons represent only a tiny fraction of GABAergic inhibitory neurons in the cortex, these neurons’ selective activation/inactivation could produce a relevant behavioral effect in the animal. Regardless of the increasing finding and discoveries on this subclass of GABAergic neurons, there is still a lot of missing information, and more studies should be done to unveil their role at the circuit and behavior level in different cortical layers and across different neocortical areas.

Cell-type-specific roles of inhibitory interneurons in the rehabilitation of auditory cortex after peripheral damage

“…Similarly, our proposed role of VIP neurons as the enablers of A1 plasticity after NIHL is consistent with previous reports showing that VIP neurons enable cortical plasticity across the sensory cortices 68,74,77,78,80-82 . In the visual cortex, synaptic transmission from VIP to SOM neurons is necessary and sufficient for the increased cortical responses in PNs after monocular deprivation in adult mice 77 .…”

A frontosensory circuit for visual context processing is synchronous in the theta/alpha band

“…In general, VIP+ interneurons are known to modulate neural activity throughout the cortex across brain-states and behaviors via a number of circuit motifs 53 . For example, VIPs play a disinhibitory role in modulating PYR neuron activity by inhibiting other interneuron types, PV and SST neurons 48, 54 . The fact that VIPs are localized in superficial cortical areas, which receive the majority of top-down inputs from higher regions, suggests that they may mediate a form of disynaptic inhibition and disynaptic dis-inhibition of multiple cell types 55 .…”

“…Consistent with our hypothesis, the cell-specific responses after top-down theta/alpha activation (6-and 10-Hz) point to a possible VIP to SST to PYR top-down disynaptic disinhibitory motif that is preferably engaged through ACa-to-V1 modulation during the oddball paradigm. This motif can be found in other areas of the cortex 18,48 , although some direct activation of PYRs during our optogenetic stimulation could result from direct synapses of ACa on PYRs 24 .…”

“…In general, VIP+ interneurons are known to modulate neural activity throughout the cortex across brain-states and behaviors via a number of circuit motifs 53 . For example, VIPs play a disinhibitory role in modulating PYR neuron activity by inhibiting other interneuron types, PV and SST neurons 48,54 .…”

“…The fact that VIPs are localized in superficial cortical areas, which receive the majority of topdown inputs from higher regions, suggests that they may mediate a form of disynaptic inhibition and disynaptic dis-inhibition of multiple cell types 55 . Evidence for such motifs have been found in multiple regions of the mouse cortex 26,43,48,[54][55][56] , and serve to elicit differential responses in brain networks depending on the task and context.…”