Updating the picture of layer 2/3 VIP-expressing interneuron function in the mouse cerebral cortex

Abstract

For years, interneurons expressing vasoactive intestinal peptide (VIP) interneurons and their function within the neocortex have been shrouded in mystery. Their relatively small size and minimal representation in the cortex have made investigation difficult. Due to their service role performed in co-operation with glia and blood vessels to supply energy during neuronal activation in the brain, the contribution of VIP interneurons to local neuronal circuit function was not appreciated. VIP interneurons in the neocortex account for roughly 12% of all interneurons. They have been described as a subgroup of the third largest population of 5-hydroxytryptamine 3a (5HT3a) receptor-expressing interneurons, non-overlapping with interneuron populations expressing parvalbumin (PV) or somatostatin (SST). However, it was recently shown that only half of VIP interneurons display a 5HT3a receptor response and a subset of VIP interneurons in visual cortex co-express SST. Over the last several years, due to new technical advancements, many facts have emerged relating to VIP interneuron phylogenetic origin, operational mechanisms within local circuits and functional significance. Some of these discoveries have dramatically shifted the perception of VIP interneurons. This review focuses on the function of the VIP interneurons residing in layer 2/3 of the mouse neocortex.

A subpopulation of cortical VIP-expressing interneurons with highly dynamic spines

“…This confirms that GFP expression had not ‘leaked’ into other inhibitory classes, which is in agreement with previous studies 37 , 48 . The relatively large proportion of co-labeling with anti-CR antibodies agrees with the finding that many VIP neurons in the upper layers of cortex are CR-expressing bipolar cells 52 , 55 , 57 , 58 . The small proportions that were co-labeled with anti-CCK and anti-NPY antibodies is also congruent with previous findings 55 – 57 .…”

“…Using 2-photon laser scanning microscope (2PLSM) in vivo we demonstrate that a subset of multipolar VIP neurons, located in superficial cortical layers, have high spine densities on their dendrites that ramify in cortical L1. Their morphological and electrophysiological characteristics are similar to the bursting type of small VIP cells 22 , 44 , 49 – 52 . Long-term imaging, over days to weeks, revealed that their spines have strikingly different dynamics as compared to spines of pyramidal neurons, displaying a higher instantaneous probability of disappearing.…”

“…Spiny GFP-positive cells that were retrospectively re-identified in brain sections, or GFP-positive cells in brain sections with spiny peri-somatic dendrites were incidentally co-labeled with anti-CCK or anti-CR antibodies (Supplementary Fig. 5 and 6 ), which indicates that they may span various VIP cell subtypes close to L1 52 , 55 , 57 .…”

Relevance of Cortical and Hippocampal Interneuron Functional Diversity to General Anesthetic Mechanisms: A Narrative Review

“…VIP + interneuron-selective interneurons show a variety of unique spiking behaviors during sustained depolarization including ''irregular'' behavior with single APs firing randomly; ''bursting'' behavior with three-five high-frequency APs discharged initially, followed by single APs at random intervals''; and ''stuttering'' behavior with clusters of spikes separated by silent periods of varying duration (Posluszny, 2019). VIP + interneurons preferentially target SST + interneurons and a fraction of PV + interneurons (Turi et al, 2019).…”

Cortical VIP+/ChAT+ interneurons: From genetics to function

“…Neurons expressing the vasoactive intestinal polypeptide (VIP) compose about 40% of the 5‐HT3aR group of cortical interneurons (Tremblay et al., 2016), and they have some intriguing features. Unlike the PV and SST interneurons, many of the VIP interneurons, whose soma is located mostly in layer 2/3 (L2/3), exhibit a bipolar dendritic morphology (Bayraktar et al., 2000; Connor & Peters, 1984; Posłuszny, 2019; Prönneke et al., 2015). Functionally, the VIP interneurons play a major role in the modulation of cortical function, especially through disinhibition of pyramidal neurons (Ayzenshtat et al., 2016; Fu et al., 2014; Karnani et al., 2016; Lee et al., 2013; Pfeffer et al., 2013; Pi et al., 2013; Walker et al., 2016).…”