Procognitive restoration of PV neuron plasticity in neurodevelopmental disorders

Abstract The hippocampus forms memories of our experiences in populations of coactive pyramidal neurons (PNs)1,2,3. Fast-spiking parvalbumin-expressing inhibitory neurons (PV INs) in the dentate gyrus–CA3/CA2 circuit of the hippocampus precisely control PN activity through mossy fibre-dependent feedforward inhibition4,5,6,7,8,9,10,11. PV INs coordinate experience-dependent changes in their intrinsic excitability, synaptic connectivity, physiology and plasticity properties9,12,13,14,15—referred to here as experience-dependent PV IN plasticity—to regulate PN activity.

PV IN impairments in early life, when neural circuitry is highly sensitive to experience, are thought to result in network hyperexcitability, seizures and impaired cognition, which are hallmarks of neurodevelopmental disorders (NDDs)16,17,18. Here we designed an input-specific translatome screen to identify regulators of experience-dependent PV IN plasticity genes (XPGs) in the CA3/CA2 subregion of adult hippocampus.