Common Principles in Functional Organization of VIP/Calretinin Cell-Driven Disinhibitory Circuits Across Cortical Areas

Abstract

In the brain, there is a vast diversity of different structures, circuitries, cell types, and cellular genetic expression profiles. While this large diversity can often occlude a clear understanding of how the brain works, careful analyses of analogous studies performed across different brain areas can hint at commonalities in neuronal organization. This in turn can yield a fundamental understanding of necessary circuitry components that are crucial for how information is processed across the brain. In this review, we outline recent in vivo and in vitro studies that have been performed in different cortical areas to characterize the vasoactive intestinal polypeptide (VIP)-and/or calretinin (CR)-expressing cells that specialize in inhibiting GABAergic interneurons. In doing so, we make the case that, across cortical structures, interneuron-specific cells commonly specialize in the synaptic disinhibition of excitatory neurons, which can ungate the integration and plasticity of external inputs onto excitatory neurons. In line with this, activation of interneuron-specific cells enhances animal performance across a variety of behavioral tasks that involve learning, memory formation, and sensory discrimination, and may represent a key target for therapeutic interventions under different pathological conditions. As such, interneuron-specific cells across different cortical structures are an essential network component for information processing and normal brain function.

Single-cell dissection of schizophrenia reveals neurodevelopmental-synaptic axis and transcriptional resilience

“…Many explanatory genes were dysregulated in a small number or only a single cell-type, or dysregulated in opposing directions across multiple cell-types, resulting in their not being identified as schizophrenia DEGs in prior studies of bulk tissue. For example, the CALB2 gene encodes the calcium binding protein calretinin which is expressed specifically in In-VIP and In-SST populations and contributes to long-term potentiation through regulation of neuronal excitability 51 , and CALB2 was specifically upregulated in only the In-VIP cell-type. ALMS1 encodes a microtubule organizing protein, and this gene was downregulated specifically in PV-expressing interneurons.…”

Alterations in Intrinsic and Synaptic Properties of Hippocampal CA1 VIP Interneurons During Aging

“…Over the last several years, the disinhibitory circuits formed by the VIP+/CR+ interneuron-specific (I-S) interneurons that innervate GABAergic cells selectively ( Acsády et al, 1996a , b ; Gulyas et al, 1996 ) and can set a balance between network excitation and inhibition, have captured the attention of neuroscientists ( Guet-McCreight et al, 2020 ). Despite their important role in coordinating hippocampal inhibition during spatial learning and goal-oriented behavior ( Magnin et al, 2019 ; Turi et al, 2019 ), very little is currently known about the survival and functioning of I-S interneurons during aging.…”

A Characterization of the Electrophysiological and Morphological Properties of Vasoactive Intestinal Peptide (VIP) Interneurons in the Medial Entorhinal Cortex (MEC)

“…This increase in IS firing pattern could be explained by the number of VIP cells that co-express CR in the MEC. Previous studies from the hippocampus (Tyan et al, 2014) and other cortical structures (Guet-McCreight et al, 2020) report an increase in the incidence of IS firing patterns when the cell co-expresses both VIP and CR. In addition to this, previous studies have also noted that VIP cells that colocalize with CR are disinhibitory in nature (Tyan et al, 2014;Turi et al, 2019;Guet-McCreight et al, 2020).…”

“…Previous studies from the hippocampus (Tyan et al, 2014) and other cortical structures (Guet-McCreight et al, 2020) report an increase in the incidence of IS firing patterns when the cell co-expresses both VIP and CR. In addition to this, previous studies have also noted that VIP cells that colocalize with CR are disinhibitory in nature (Tyan et al, 2014;Turi et al, 2019;Guet-McCreight et al, 2020). From our IHC experiments, we find that 67.59% of the total tdTom cells colocalize with CR.…”

“…These cells are known to target both PV and SOM inhibitory cells as well as excitatory cells in various structures (Kepecs and Fishell, 2014;Batista-Brito et al, 2017;Kuchibhotla et al, 2017;Rhomberg et al, 2018;Krabbe et al, 2019;Garcia-Junco-Clemente et al, 2019). Thus, VIP interneurons are well-positioned to provide transient and selective breaks in the E/I balance by disinhibiting excitatory cells in other cortical regions (Letzkus et al, 2015;Guet-McCreight et al, 2020). The disinhibitory circuit motif has been well defined in the hippocampus (Tyan et al, 2014;Turi et al, 2019), auditory cortex (Pi et al, 2013), basolateral amygdala (Rhomberg et al, 2018;Krabbe et al, 2019), visual cortex (Pfeffer et al, 2013;Batista-Brito et al, 2017), and somatosensory cortex (Bayraktar et al, 2000;Lee et al, 2013;Prönneke et al, 2015).…”