The Role of Inhibitory Interneurons in Cortical Computation: Mechanisms, Functions, and Clinical Implications

Cortical computation relies on the precise coordination of excitatory and inhibitory activity across neural circuits. Inhibitory interneurons, particularly those expressing parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP), form distinct but interconnected subnetworks that sculpt cortical dynamics. These interneuron subtypes exhibit specialized connectivity patterns and firing properties that enable them to regulate critical processes such as oscillatory synchronization, sensory gating, and excitation-inhibition (E/I) balance. PV+ interneurons are central to gamma oscillations and spike-timing control. SOM+ cells modulate dendritic integration and synaptic plasticity; while VIP+ interneurons exert disinhibitory control over other inhibitory cells, dynamically adjusting network responsiveness. Dysfunctions in these circuits are implicated in a range of neuropsychiatric and neurological disorders, including schizophrenia, epilepsy, and autism spectrum conditions. Progress in optogenetics, genetic engineering, and neural circuit analysis has deepened our understanding of interneuron diversity, emphasizing their crucial roles in cognitive function and neurological disorders. This review synthesizes current findings on the cellular, circuit, and computational functions of PV+, SOM+, and VIP+ interneurons, emphasizing their integrative roles in cortical processing and their emerging relevance as therapeutic targets.