UCLA

During so-called critical periods of early postnatal life, sensory experience profoundly and permanently sculpts cortical neural circuitry. After critical period closure, experience-dependent plasticity is dramatically limited, and it is not known what differentiates juvenile and adult plasticity mechanisms. At its core, plasticity is a dendritic phenomenon, and in the cortex, plasticity is determined by changes in sensory input and cortical state. Here we show that dendritic and somatic activity in pyramidal neurons is fundamentally different across critical period closure due to the cholinergic engagement of inhibitory circuitry. At the peak of the critical period, acetylcholine released from the basal forebrain directly excites somatostatin-expressing (SST) interneurons. The resultant inhibition of pyramidal cell dendrites and of fast-spiking, parvalbumin-expressing (PV) inhibitory neurons enhances branch-specific dendritic responses and increases somatic spiking within pyramidal neurons. By adulthood, SST cells lose cholinergic excitability, and inhibition becomes inverted along the somatodendritic axis, with less SST-mediated dendritic inhibition and more PV-mediated somatic inhibition. When SST cells are optogenetically activated in adult cortex, branch-specific dendritic activity and somatic disinhibition re-emerge. Conversely, suppressing SST cell activity during the critical period prevents the normal development of binocular receptive fields by impairing the experience-dependent maturation of ipsilateral eye inputs. These data reveal a transient circuit through which inhibition and neuromodulation converge to facilitate experience-dependent plasticity by shaping dendritic and somatic activity.