Synaptic plasticity of prefrontal long-range inhibition regulates cognitive flexibility.

Potentiation of callosal GABAergic synapses from prefrontal PV neurons onto corticothalamic neurons is linked to cognitive flexibility during rule shifts.

• Why it matters: Understanding the behavioral significance of synaptic plasticity at cortical GABAergic synapses is crucial, as it may reveal mechanisms underlying higher-order cognition and related disorders.
• What they did: The study used behavioral optogenetics and patch-clamp electrophysiology to examine how learning extradimensional rule shifts affects GABAergic synapse potentiation, specifically targeting callosal PV neuron connections.
• The result: Disrupting this potentiation causes perseveration, while restoring it with gamma-frequency stimulation reestablishes flexible behavior, highlighting a plasticity locus that influences normal and pathological cognition.