Inhibitory circuit gating of auditory critical-period plasticity.

Abstract

SUMMARYCortical sensory maps are remodeled during early life to adapt to the surrounding environment. Both sensory and contextual signals play an important role, but how these two inputs converge to sculpt developing thalamocortical circuits remains largely unknown. Here, we reveal layer 1 (L1) of primary auditory cortex (A1) to be a key hub where neuromodulatory and topographically-organized thalamic inputs meet to tune the cortical layers below. Inhibitory interneurons in L1 send narrowly descending projections to differentially modulate thalamic drive onto pyramidal and parvalbumin-expressing (PV) cells in L4, creating brief windows of intracolumnar activation. Silencing L1 (but not VIP) cells abolishes map plasticity during the tonotopic critical period. Instead, developmental transitions of nicotinic acetylcholine receptor (nAChR) sensitivity in these cells by the Lynx1 protein can be overridden to extend critical period closure. Notably, thalamocortical maps in L1 are themselves stable, serving as a scaffold for cortical plasticity throughout life.