Oscillatory Activity in Developing Prefrontal Networks Results from Theta-Gamma-Modulated Synaptic Inputs

The hippocampus-driven entrainment of neonatal prefrontal circuits in theta-gamma oscillations contributes to the maturation of cognitive abilities, yet the underlying synaptic mechanisms are still unknown. Here we combine patch-clamp recordings from morphologically and neurochemically characterized layer V pyramidal neurons and interneurons in vivo, with extracellular recordings from the prelimbic cortex (PL) of awake and lightly anesthetized neonatal rats, to elucidate the synaptic framework of early network oscillations. We demonstrate that all neurons spontaneously fire bursts of action potentials. They receive barrages of fast and slow glutamatergic as well as GABAergic synaptic inputs. Oscillatory theta activity results from long-range coupling of pyramidal neurons, presumably within prelimbic-hippocampal circuits, and from local interactions between interneurons. In contrast, beta-low gamma activity requires external glutamatergic drive on prelimbic interneurons. High-frequency oscillations in layer V are independent of interactions at chemical synapses. Thus, specific theta-gamma-modulated synaptic interactions represent the substrate of network oscillations in the developing PL.