Gamma rhythms link prefrontal interneuron dysfunction with cognitive inflexibility in Dlx5/6+/− mice

摘要: Abnormalities in GABAergic interneurons, particularly fast-spiking interneurons (FSINs) that generate gamma (γ; ∼30-120 Hz) oscillations, are hypothesized to disrupt prefrontal cortex (PFC)-dependent cognition schizophrenia. Although γ rhythms abnormal schizophrenia, it remains unclear whether they directly influence cognition. Mechanisms underlying schizophrenia's typical post-adolescent onset also remain elusive. We addressed these issues using mice heterozygous for Dlx5/6, which regulate interneuron development. In Dlx5/6(+/-) mice, FSINs become following adolescence, coinciding with the of cognitive inflexibility and deficient task-evoked oscillations. Inhibiting PFC control reproduced deficits, whereas stimulating them at γ-frequencies restored flexibility adult mice. These pro-cognitive effects were frequency specific persistent. findings elucidate a mechanism whereby FSIN development may contribute schizophrenia endophenotypes. Furthermore, demonstrate causal, potentially therapeutic, role interneuron-driven oscillations domains core