Cholinergic Modulation of Dendritic Signaling in Hippocampal GABAergic Inhibitory Interneurons

Dendrites represent the "reception hub" of the neuron as they collect thousands of different inputs and send a coherent response to the cell body. A considerable portion of these signals, especially in vivo, arises from neuromodulatory sources, which affect dendritic computations and cellular activity. In this context, acetylcholine (ACh) exerts a coordinating role of different brain structures, contributing to goal-driven behaviors and sleep-wake cycles. Specifically, cholinergic neurons from the medial septum-diagonal band of Broca complex send numerous projections to glutamatergic principal cells and GABAergic inhibitory neurons in the hippocampus, differentially entraining them during network oscillations. Interneurons display abundant expression of cholinergic receptors and marked responses to stimulation by ACh. Nonetheless, the precise localization of ACh inputs is largely unknown, and evidence for cholinergic modulation of interneuronal dendritic signaling remains elusive. In this article, we review evidence that suggests modulatory effects of ACh on dendritic computations in three hippocampal interneuron subtypes: fast-spiking parvalbumin-positive (PV⁺) cells, somatostatin-expressing (SOM⁺) oriens lacunosum moleculare cells and vasoactive intestinal polypeptide-expressing (VIP⁺) interneuron-selective interneurons. We consider the distribution of cholinergic receptors on these interneurons, including information about their specific somatodendritic location, and discuss how the action of these receptors can modulate dendritic Ca²⁺ signaling and activity of interneurons. The implications of ACh-dependent Ca²⁺ signaling for dendritic plasticity are also discussed. We propose that cholinergic modulation can shape the dendritic integration and plasticity in interneurons in a cell type-specific manner, and the elucidation of these mechanisms will be required to understand the contribution of each cell type to large-scale network activity.