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.

Keywords: behavior; cerebral cortex; disinhibition; hippocampus; interneuron; microcircuit; vasoactive intestinal polypeptide.

Figure 1

Interneuron-specific cell circuitry across cortical areas allows disinhibition and synaptic potentiation of pyramidal cells via external inputs. In these schematic figures, we highlight the commonalities in I-S circuitry across (A) CA1 hippocampus, and (B) neocortex. We chose to provide illustrations for these brain regions because enough details on I-S cell circuitry in these areas have been reported in the literature. Red shapes denote increased neural activation, and blue shapes denote decreased neural activation. The flow of each schematic is the following: increased activation of excitation from external inputs (1st red arrow) increases activation of I-S cells (2nd red arrow), which decreases activity of other local SOM+ and PV+ cell types (blue arrow), and allows an increase in gain in pyramidal cells (3rd red arrow). In principle, this can be generalized as the basic mechanism through which activation of I-S cells in different brain areas can lead to enhancements in learning, memory, and sensory discrimination. SO/A, Stratum Oriens/Alveus; SP, Stratum Pyramidale; SR, Stratum Radiatum; SLM, Stratum Lacunosum Moleculare; PYR, Pyramidal neuron.