Cortical disinhibitory circuits: cell types, connectivity and function

In neural circuits, disinhibition (or inhibition of inhibition) commonly operates in the form of two inhibitory neurons connected to one another in series. Disinhibition requires an inhibitory neuron in an active state such that the activity of this neuron can be inhibited. Across cortical brain regions, synaptic connections between GABAergic inhibitory interneurons create multiple opportunities for circuit disinhibition, which are determined in part by the activity state of the connected interneurons. Although interneurons that express VIP have been largely considered to be disinhibitory, they are a heterogeneous cell population in which distinct subtypes likely participate in distinct inhibitory and disinhibitory microcircuits. A key disinhibitory circuit motif that has been documented across cortical areas implicates inhibition of the interneurons that innervate the distal dendrites of principal cells, such as hippocampal oriens–lacunosum moleculare cells and neocortical Martinotti cells. Mechanistic studies linking cell types to function will be necessary to further clarify the roles of distinct disinhibitory circuits in cortical computations and cognitive functions. The concept of a dynamic excitation/inhibition balance tuned by circuit disinhibition, which can shape information flow during complex behavioral tasks, has arisen as an important and conserved information-processing motif. In cortical circuits, different subtypes of GABAergic inhibitory interneurons are connected to each other, offering an anatomical foundation for disinhibitory processes. Moreover, a subpopulation of GABAergic cells that express vasoactive intestinal polypeptide (VIP) preferentially innervates inhibitory interneurons, highlighting their central role in disinhibitory modulation. We discuss inhibitory neuron subtypes involved in disinhibition, with a focus on local circuits and long-range synaptic connections that drive disinhibitory function. We highlight multiple layers of disinhibition across cortical circuits that regulate behavior and serve to maintain an excitation/inhibition balance. The concept of a dynamic excitation/inhibition balance tuned by circuit disinhibition, which can shape information flow during complex behavioral tasks, has arisen as an important and conserved information-processing motif. In cortical circuits, different subtypes of GABAergic inhibitory interneurons are connected to each other, offering an anatomical foundation for disinhibitory processes. Moreover, a subpopulation of GABAergic cells that express vasoactive intestinal polypeptide (VIP) preferentially innervates inhibitory interneurons, highlighting their central role in disinhibitory modulation. We discuss inhibitory neuron subtypes involved in disinhibition, with a focus on local circuits and long-range synaptic connections that drive disinhibitory function. We highlight multiple layers of disinhibition across cortical circuits that regulate behavior and serve to maintain an excitation/inhibition balance.