{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:48:26Z","timestamp":1777283306385,"version":"3.51.4"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Synaptic Neurosci."],"abstract":"<jats:p>Experience reshapes cortical circuits, yet plasticity is tightly gated\u2014high during early critical periods and increasingly constrained with maturation. Later in life, aging and Alzheimer\u2019s disease (AD) create a growing demand to restrain network hyperactivity. Across these contexts, excitatory drive onto parvalbumin-positive fast-spiking interneurons (PVs)\u2014shaped by synaptic organizers such as NPTX2\u2014offers 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\u2192PV 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.<\/jats:p>","DOI":"10.3389\/fnsyn.2026.1819500","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:52:09Z","timestamp":1777279929000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tuning excitatory input to fast-spiking parvalbumin-positive interneurons: a lever for plasticity and hyperexcitability across the lifespan"],"prefix":"10.3389","volume":"18","author":[{"given":"Daniel","family":"Severin","sequence":"first","affiliation":[{"name":"Mind\/Brain Institute, Johns Hopkins University","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"Mind\/Brain Institute, Johns Hopkins University","place":["Baltimore, MD, United States"]},{"name":"Department of Neurosciences, Johns Hopkins University","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"tgaa026","DOI":"10.1093\/texcom\/tgaa026","article-title":"A composite sketch of fast-spiking parvalbumin-positive neurons","volume":"1","author":"Bartholome","year":"2020","journal-title":"Cereb. 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