Principles of GABAergic signaling in developing cortical network dynamics

GABAergic signaling provides inhibitory stabilization and spatiotemporally coordinates the firing of recur-rently connected excitatory neurons in mature cortical circuits. Inhibition thus enables self-generated neuronal activity patterns that underlie various aspects of sensation and cognition. In this review, we aim to provide a conceptual framework describing how and when GABA-releasing interneurons acquire their network functions during development. Focusing on the developing visual neocortex and hippocampus in mice and rats in vivo, we hypothesize that at the onset of patterned activity, glutamatergic neurons are stable by themselves and inhibitory stabilization is not yet functional. We review important milestones in the devel-opment of GABAergic signaling and illustrate how the cell-type-specific strengthening of synaptic inhibition toward eye opening shapes cortical network dynamics and allows the developing cortex to progressively disengage from extra-cortical synaptic drive. We translate this framework to human cortical development and discuss clinical implications for the treatment of neonatal seizures.

Automated summary

GABAergic signaling plays a crucial role in the inhibitory stabilization and coordination of excitatory neurons in mature cortical circuits. This review examines how GABA-releasing interneurons acquire their network functions during development, focusing on the visual neocortex and hippocampus in mice and rats. The authors propose that inhibitory stabilization is not functional at the onset of patterned activity, and that glutamatergic neurons are stable by themselves. The strengthening of inhibitory synaptic transmission toward eye opening shapes cortical network dynamics and allows the developing cortex to disengage from extra-cortical synaptic drive. The framework presented in this review has implications for our understanding of human cortical development and the treatment of neonatal seizures.