Tuning excitatory input to fast-spiking parvalbumin-positive interneurons: a lever for plasticity and hyperexcitability across the lifespan

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Experience reshapes cortical circuits, yet plasticity is tightly gated—high during early critical periods and increasingly constrained with maturation. Later in life, aging and Alzheimer’s disease (AD) create a growing demand to restrain network hyperactivity. Across these contexts, excitatory drive onto parvalbumin-positive fast-spiking interneurons (PVs)—shaped by synaptic organizers such as NPTX2—offers a control point for tuning inhibitory tone while preserving fast, precise inhibition. We outline the cellular and synaptic specializations that make PVs powerful regulators of network excitability, then synthesize evidence from visual cortex suggesting that critical period termination reflects the loss of plasticity at principal neuron→PV inputs. Finally, we extend this framework to aging and AD, where medial temporal lobe hyperactivity and early PV dysfunction coincide with NPTX2 dysregulation, suggesting that restoring excitatory recruitment of PVs may help stabilize circuits and prevent cognitive decline.

This publication has 88 references indexed in Scilit: