"Maestro" Hub Neurons Orchestrate the Immature GABA Network Symphony.

Commentary Coordinated activation of neural networks is associated with most complex brain function in adults, and has been implicated in the maturation of neural circuits postnatally. Production of orchestrated neural population activity involves changes in cellular excitability, superimposed on synaptic and extra-synaptic communication characteristics that, in turn, require specific network architecture. In particular, gamma frequency oscillations (GFOs) involve relatively high frequency activity (> 40 Hz), transiently generated by repetitive and synchronized activity of relatively large groups of neurons, resulting in a fluctuating period of increased and decreased excitability in target neuron populations (1, 2). These GFOs can also be coordinated across multiple networks almost simultaneously, providing a substrate for synchronization of activity across brain regions. Interestingly, GFOs often precede seizures and ictal-like activity and may, therefore, be an electrographic hallmark of chronic epilepsy. Synaptic interactions between excitatory glutamatergic and inhibitory GABAergic neurons can contribute to generation of GFOs—and seizures—in the adult brain. Experimental data indicate that GFOs in cortical areas, including the hippocampus, can also be generated and coordinated across regions by interconnected GABAergic neurons in the immature brain; these data are well-supported by theoretical models (1). Coordinated activation of neuronal assemblies, such as that revealed by population oscillations (i.e., GFOs), has been proposed to involve superconnected nodes (i.e., " hubs ") of local networks, in which a few so-called hub neurons link nodes via long-range connections (3). Both within and between networks, GABAergic neurons appear to fulfill this role (2). The work by Quilichini and Le Van Quyen et al. aims to better understand the mechanisms of GFO generation , including the potential involvement of hub cells that might trigger GFO generation, as well as the relationship of GFOs to ictal-like activity in immature hippocampal networks, where GABA neurons appear to be the predominant substrate of network function. The authors investigated oscillations in immature mice and rats at an age when pyramidal cells are immature, ion cotrans-porter balance has not been established as it is in adults, and in which GABA tends to be excitatory. They used an in vitro septohippocampal preparation that allowed for study of local excitability within discreet regions of the hippocampus, as well as communication between distinct cell assemblies. Using recording conditions designed to evoke epileptiform activity in the preparation, the authors recorded activity of neuron populations as well as synaptic input to individual neurons within a population. These strategies allowed recordings from multiple hippocampal …