Developing networks follow common rules to shift from silent cells to coactive networks that operate via thousands of synapses. This review deals with some of these rules and in particular those concerning the crucial role of the neurotransmitter γ-aminobuytric acid (GABA), which operates primarily via chloride-permeable GABA_Areceptor channels. In all developing animal species and brain structures investigated, neurons have a higher intracellular chloride concentration at an early stage leading to an efflux of chloride and excitatory actions of GABA in immature neurons. This triggers sodium spikes, activates voltage-gated calcium channels, and acts in synergy with NMDA channels by removing the voltage-dependent magnesium block. GABA signaling is also established before glutamatergic transmission, suggesting that GABA is the principal excitatory transmitter during early development. In fact, even before synapse formation, GABA signaling can modulate the cell cycle and migration. The consequence of these rules is that developing networks generate primitive patterns of network activity, notably the giant depolarizing potentials (GDPs), largely through the excitatory actions of GABA and its synergistic interactions with glutamate signaling. These early types of network activity are likely required for neurons to fire together and thus to “wire together” so that functional units within cortical networks are formed. In addition, depolarizing GABA has a strong impact on synaptic plasticity and pathological insults, notably seizures of the immature brain. In conclusion, it is suggested that an evolutionary preserved role for excitatory GABA in immature cells provides an important mechanism in the formation of synapses and activity in neuronal networks.

Coordinating Neuronal Assemblies: Theoretical models predict the existence of so-called hub neurons—highly connected cells that strongly influence the synchronization of spiking activity in a large group of neurons. However, experimental evidence for the existence of these neuronal hubs is lacking. Bonifazi et al. (p. 1419 ) used high-resolution, two-photon calcium imaging to measure spontaneous calcium fluctuations in hundreds of neurons simultaneously and determined the relative timing of these fluctuations. Examination of functional connectivity maps, based on temporal correlation measurements, revealed a subpopulation of GABAergic hub neurons displaying a remarkably widespread axonal arborization that orchestrated network synchrony in developing hippocampal networks. Spontaneous network synchronizations in developing hippocampus caused giant depolarizing potentials in individual neurons, and manipulating the spike activity in potential hub cells influenced network activity.