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

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.