The rapid developmental rise of somatic inhibition disengages hippocampal dynamics from self-motion

ABSTRACT Early electrophysiological brain oscillations recorded in preterm babies and newborn rodents are initially mostly ignited by bottom-up sensorimotor activity and only later can detach from external inputs. This is a hallmark of most developing brain areas including the hippocampus, which in the adult brain, functions in integrating external inputs onto internal dynamics. Such developmental disengagement from external inputs is likely a fundamental step for the proper development of cognitive internal models. Despite its importance, the exact timing and circuit basis for this disengagement remain unknown. To address this issue, we have investigated the daily evolution of CA1 dynamics and underlying circuits during the first and second postnatal week of mouse development using a combination of two-photon calcium imaging of neuronal somata and axons in non-anesthetized pups, viral tracing and chemogenetics. We show that the first postnatal week ends with an abrupt switch in the representation of self-motion in CA1. Indeed, most CA1 pyramidal cells switch from activated to inhibited by self-generated movements at the end of the first postnatal week whereas GABAergic neurons remain positively modulated throughout this period. This rapid switch occurs within two days and is mediated by the rapid anatomical and functional surge of somatic inhibition. The observed dynamics is consistent with a two-population model undergoing strengthening inhibition. Remarkably, a transient silencing of local somatostatin-expressing interneurons both prevents the emergence of the perisomatic GABAergic coverage and the disengagement of CA1 hippocampal dynamics from self-motion. We propose that such activity-dependent emergence of feedback inhibitory circuits critically inaugurates the development of internal cognitive models.