ArticlebioRxiv : the preprint server for biology2025
Synaptic plasticity of prefrontal long-range inhibition regulates cognitive flexibility.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
While glutamatergic synaptic plasticity is believed to be a fundamental mechanism mediating learning, the behavioral significance of plasticity at cortical GABAergic synapses remains less well understood. Furthermore, despite recent discoveries of long-range projections from neocortical GABAergic neurons, details about how they function are also sparse. Here we combine behavioral optogenetics with patch-clamp electrophysiology to link plasticity at long-range GABAergic synapses with higher-order cognitive functions. Specifically, learning extradimensional rule shifts potentiates callosal GABAergic synapses from prefrontal parvalbumin-expressing (PV) neurons onto corticothalamic neurons. Disrupting this potentiation by inhibiting callosal PV terminals during rule shifts induces perseveration, whereas reinstating this potentiation with subsequent gamma-frequency callosal PV terminal stimulation restores flexible behavior. This shows how a novel plasticity locus can regulate brain circuits underlying normal cognition and pathological states.
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