Mouse hippocampal CA1 VIP interneurons detect novelty in the environment and support recognition memory.

In the CA1 hippocampus, vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) play a prominent role in disinhibitory circuit motifs. However, the specific behavioral conditions that lead to circuit disinhibition remain uncertain. To investigate the behavioral relevance of VIP-IN activity, we employed wireless technologies allowing us to monitor and manipulate their function in freely behaving mice. Our findings reveal that, during spatial exploration in new environments, VIP-INs in the CA1 hippocampal region become highly active, facilitating the rapid encoding of novel spatial information. Remarkably, both VIP-INs and pyramidal neurons (PNs) exhibit increased activity when encountering novel changes in the environment, including context- and object-related alterations. Concurrently, somatostatin- and parvalbumin-expressing inhibitory populations show an inverse relationship with VIP-IN and PN activity, revealing circuit disinhibition that occurs on a timescale of seconds. Thus, VIP-IN-mediated disinhibition may constitute a crucial element in the rapid encoding of novelty and the acquisition of recognition memory.

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

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.

Synaptic Mechanisms Underlying the Network State-Dependent Recruitment of VIP-Expressing Interneurons in the CA1 Hippocampus.

Disinhibition is a widespread circuit mechanism for information selection and transfer. In the hippocampus, disinhibition of principal cells is provided by the interneuron-specific interneurons that express the vasoactive intestinal polypeptide (VIP-IS) and innervate selectively inhibitory interneurons. By combining optophysiological experiments with computational models, we determined the impact of synaptic inputs onto the network state-dependent recruitment of VIP-IS cells. We found that VIP-IS cells fire spikes in response to both the Schaffer collateral and the temporoammonic pathway activation. Moreover, by integrating their intrinsic and synaptic properties into computational models, we predicted recruitment of these cells between the rising phase and peak of theta oscillation and during ripples. Two-photon Ca2+-imaging in awake mice supported in part the theoretical predictions, revealing a significant speed modulation of VIP-IS cells and their preferential albeit delayed recruitment during theta-run epochs, with estimated firing at the rising phase and peak of the theta cycle. However, it also uncovered that VIP-IS cells are not activated during ripples. Thus, given the preferential theta-modulated firing of VIP-IS cells in awake hippocampus, we postulate that these cells may be important for information gating during spatial navigation and memory encoding.