Spontaneous synchronous network activity in the neonatal development of mPFC in mice

Spontaneous Synchronous Network Activity (SSA) is a hallmark of neurodevelopment found in numerous central nervous system structures, including neocortex. SSA occurs during restricted developmental time-windows, commonly referred to as critical periods in sensory neocortex. Although part of the neocortex, the critical period for SSA in the medial prefrontal cortex (mPFC) and the underlying mechanisms for generation and propagation are unknown. Using Ca²⁺ imaging and whole-cell patch-clamp in an acute mPFC slice mouse model, the development of spontaneous activity and SSA was investigated at cellular and network levels during the two first postnatal weeks. The data revealed that developing mPFC neuronal networks are spontaneously active and exhibit SSA in the first two postnatal weeks, with peak synchronous activity at postnatal days (P)8-9. Networks remain active but are desynchronized by the end of this 2-week period. SSA was driven by excitatory ionotropic glutamatergic transmission with a small contribution of excitatory GABAergic transmission at early time points. The neurohormone oxytocin desynchronized SSA in the first postnatal week only without affecting concurrent spontaneous activity. By the end of the second postnatal week, inhibiting GABA_A receptors restored SSA. These findings point to the emergence of GABA_A receptor-mediated inhibition as a major factor in the termination of SSA in mouse mPFC.