Embryonically active piriform cortex neurons promote intracortical recurrent connectivity during development

Neuronal activity plays a critical role in the maturation of circuits that propagate sensory information into the brain. How widely does early activity regulate circuit maturation across the developing brain? Here, we used targeted recombination in active populations (TRAP) to perform a brain-wide survey for prenatally active neurons in mice and identified the piriform cortex as an abundantly TRAPed region. Whole-cell recordings in neonatal slices revealed preferential interconnectivity within embryonically TRAPed piriform neurons and their enhanced synaptic connectivity with other piriform neurons. In vivo Neuropixels recordings in neonates demonstrated that embryonically TRAPed piriform neurons exhibit broad functional connectivity within piriform and lead spontaneous synchronized population activity during a transient neonatal period, when recurrent connectivity is strengthening. Selectively activating or silencing these neurons in neonates enhanced or suppressed recurrent synaptic strength, respectively. Thus, embryonically TRAPed piriform neurons represent an interconnected hub-like population whose activity promotes recurrent connectivity in early development. •Brain-wide screen for prenatal neuronal activity highlights mouse piriform cortex•Embryonically active piriform neurons have hub-like connectivity ex vivo and in vivo•Neuropixels recordings show hub-like neurons lead population bursts in neonates•Altering neonatal hub-like neuronal activity modulates developing recurrent circuitry Using TRAP to perform a brain-wide screen for embryonically active neurons, Wang et al. identify and demonstrate the transient developmental role of activity in a hub-like neuronal population in promoting recurrent connectivity in the piriform cortex. These findings suggest a mechanism of activity-dependent maturation of intracortical circuits.