VIP NEURON SUBTYPES DIFFERENTIALLY PROVIDE INHIBITORY INPUT ONTO EXCITATORY NEURONS ACROSS LAYERS IN MOUSE BARREL CORTEX

Cortical computations depend on layer- and cell-type–specific microcircuits in which inhibitory interneurons shape excitatory activity with high temporal and spatial precision. VIP interneurons are often described as primarily disinhibitory because they preferentially inhibit other interneurons, yet multiple lines of evidence indicate that VIP cells can also provide direct inhibition to excitatory neurons. Because VIP neurons are heterogeneous, it remains unclear which marker-defined VIP subtypes deliver inhibitory input to excitatory neurons across cortical layers. Here, we used an intersectional Flp/Cre genetic strategy (Ai80; membrane-targeted opsin) and whole-cell voltage-clamp recordings from excitatory neurons across layers in mouse barrel cortex, in order to quantify light-evoked IPSCs following subtype-specific stimulation of three VIP subtypes (VIP-CCK, VIP-CR, and VIP-ChAT). In our current dataset, VIP-CCK stimulation evoked IPSCs broadly in L2 (22/27), L4 (15/16), and L5 (18/18) excitatory neurons. In contrast, VIP-ChAT stimulation evoked IPSCs predominantly in L5 excitatory neurons (5/6), with no detectable responses in L2 (0/23) or L4 (0/4). VIP-CR stimulation evoked IPSCs in L4 (6/6) and L5 (3/3) excitatory neurons but not L2 (0/9). Together, these findings reveal pronounced subtype- and layer-specific inhibitory output from VIP interneurons onto excitatory neurons, supporting distinct circuit roles for VIP-CCK, VIP-CR, and VIP-ChAT subtypes.
Supported by DFG (STA 431/21-1)