Subcellular Targeting of VIP Boutons in Mouse Barrel Cortex is Layer-Dependent and not Restricted to Interneurons

Abstract

Neocortical vasoactive intestinal polypeptide (VIP) expressing cells are a diverse subpopulation of GABAergic interneurons issuing distinct axonal projections. They are known to inhibit other types of interneurons as well as excitatory principal neurons and possess a disinhibitory net effect in cortical circuits. In order to elucidate their targeting specificity, the output connectivity of VIP interneurons was studied at the subcellular level in barrel cortex of interneuron-specific Cre-driver mice, using pre- and postembedding electron microscopy. Systematically sampling VIP boutons across all layers, we found a substantial proportion of the innervated subcellular structures were dendrites (80%), with somata (13%), and spines (7%) being much less targeted. In layer VI, a high proportion of axosomatic synapses was found (39%). GABA-immunopositive ratio was quantified among the targets using statistically validated thresholds: only 37% of the dendrites, 7% of the spines, and 26% of the somata showed above-threshold immunogold labeling. For the main target structure “dendrite”, a higher proportion of GABAergic subcellular profiles existed in deep than in superficial layers. In conclusion, VIP interneurons innervate non-GABAergic excitatory neurons and interneurons at their subcellular domains with layer-dependent specificity. This suggests a diverse output of VIP interneurons, which predicts multiple functionality in cortical circuitry beyond disinhibition.

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).…”

Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention

“…Recent anatomical and functional evidence shows that VIP interneurons in rodent brain are morphologically and functionally diverse and that prefrontal cortical VIP cells can directly target pyramidal neurons 47–49 . Both multipolar and bipolar VIP cells form synapses on apical and basal dendrites of pyramidal neurons in superficial and deep layers and VIP neurons directly inhibit pyramidal neuron firing 48,49 . Frontal cortical VIP cells rapidly and directly inhibit pyramidal neurons, while they can also indirectly excite these pyramidal neurons via parallel disinhibition.…”

Learning-induced plasticity in the barrel cortex is disrupted by inhibition of layer 4 somatostatin-containing interneurons

“…although the axonal tree of L2/3 VIP-INs is observed across all layers of the mouse barrel cortex, including L4, their axonal boutons are predominant in L2/3 and 5a, being rather rare in L4, at 42.8%, 22.3% and 13.3% (Prönneke et al, 2015). Additionally, in L4, only 34% of the VIP-IN axonal boutons are located on GABA+ dendrites, suggesting weak inhibitory-inhibitory interactions in this layer (Zhou et al, 2017). Muñoz et al (2017) (Fu et al, 2015), and whisker-based object localization in the go/no-go task increases the spike rates of VIP-INs in the barrel cortex (Yu et al, 2019).…”