Differential Inputs to the Perisomatic and Distal-Dendritic Compartments of VIP-Positive Neurons in Layer 2/3 of the Mouse Barrel Cortex

Abstract

The recurrent network composed of excitatory and inhibitory neurons is fundamental to neocortical function. Inhibitory neurons in the mammalian neocortex are molecularly diverse, and individual cell types play unique functional roles in the neocortical microcircuit. Recently, vasoactive intestinal polypeptide-positive (VIP+) neurons, comprising a subclass of inhibitory neurons, have attracted particular attention because they can disinhibit pyramidal cells through inhibition of other types of inhibitory neurons, such as parvalbumin- (PV+) and somatostatin-positive (SOM+) inhibitory neurons, promoting sensory information processing. Although VIP+ neurons have been reported to receive synaptic inputs from PV+ and SOM+ inhibitory neurons as well as from cortical and thalamic excitatory neurons, the somatodendritic localization of these synaptic inputs has yet to be elucidated at subcellular spatial resolution. In the present study, we visualized the somatodendritic membranes of layer (L) 2/3 VIP+ neurons by injecting a newly developed adeno-associated virus (AAV) vector into the barrel cortex of VIP-Cre knock-in mice, and we determined the extensive ramification of VIP+ neuron dendrites in the vertical orientation. After immunohistochemical labeling of presynaptic boutons and postsynaptic structures, confocal laser scanning microscopy revealed that the synaptic contacts were unevenly distributed throughout the perisomatic (<100 μm from the somata) and distal-dendritic compartments (≥100 μm) of VIP+ neurons. Both corticocortical and thalamocortical excitatory neurons preferentially targeted the distal-dendritic compartment of VIP+ neurons. On the other hand, SOM+ and PV+ inhibitory neurons preferentially targeted the distal-dendritic and perisomatic compartments of VIP+ neurons, respectively. Notably, VIP+ neurons had few reciprocal connections. These observations suggest different inhibitory effects of SOM+ and PV+ neuronal inputs on VIP+ neuron activity; inhibitory inputs from SOM+ neurons likely modulate excitatory inputs locally in dendrites, while PV+ neurons could efficiently interfere with action potential generation through innervation of the perisomatic domain of VIP+ neurons. The present study, which shows a precise configuration of site-specific inputs, provides a structural basis for the integration mechanism of synaptic inputs to VIP+ neurons.

Vasoactive Intestinal Polypeptide-Immunoreactive Interneurons within Circuits of the Mouse Basolateral Amygdala

“…Genetic targeting and optical activation enabled us to demonstrate that VIP+ IS-INs give rise to GABA A receptor-mediated postsynaptic responses in several BLA INs. Previous studies in the neocortex and hippocampus have consistently shown that VIP+ INs form synapses onto PV+ and SOM+ INs ( Lee et al, 2013 ; Pfeffer et al, 2013 ; Pi et al, 2013 ; Sohn et al, 2016 ). Likewise, a recent report described how BLA VIP+ INs also innervate both PV+ and SOM+ INs ( Krabbe et al, 2016 ).…”

“…In the rat BLA, Muller and colleagues (2003) reported synaptic connections between Calbindin+ INs and VIP+ INs. Previous reports in the neocortex have shown that VIP+ INs have strong reciprocal connections with PV+ ( Staiger et al, 1997 ; Hioki et al, 2013 ; Sohn et al, 2016 ) and SOM+ INs ( Lee et al, 2013 ; Pfeffer et al, 2013 ; Pi et al, 2013 ; Sohn et al, 2016 ). Future studies will have to determine whether VIP+ INs in the BLA also preferentially interconnect with PV+ and/or SOM+ INs.…”

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

“…So far, morphological studies have quantified the connectivity between VIP interneurons and other types of interneurons and showed that it varied among different subcellular compartments and target cells ( Staiger et al 2004 ; Dávid et al 2007 ; Hioki et al 2013 ; Sohn et al 2016 ). Studies on the output of the partially overlapping population of CR interneurons found differential innervation patterns throughout cortical layers of rodent and monkey V1: in superficial layers, they primarily inhibit interneurons, while in deep layers they preferentially inhibit pyramidal neurons ( Meskenaite 1997 ; Gonchar and Burkhalter 1999 ).…”

Post-mitotic Prox1 expression controls the final specification of cortical VIP interneuron subtypes

“…The two subtypes tend to sit in different parts of L2/3, with VIP multipolar cells often found close to the border to L1, while VIP bipolar cells usually are located closer to L4 (He et al, 2016). In combination with their distinct dendritic architecture, this could determine the origin of inputs the VIP subtypes receive (Sohn et al, 2016). Additionally, the distinct glutamate receptor composition expressed by the two VIP subtypes (Paul et al, 2017) could also point to cell selective synaptic wiring.…”