GABAergic neurons are major contributors of network inhibition in the neonatal hippocampus in-vivo

During development, neural network maturation is activity dependent. During the neonatal period, activity is provided by intermittent, spontaneous network activity patterns (SNAP) that occur independently of environment stimuli. Among the neurotransmitters that take part in neonatal development, the Gamma-amino-butyric acid (GABA) plays a pivotal role. GABAergic cells are the first to emerge the first to form functional synapses. GABA antagonists block hippocampal SNAPs in-vitro and alterations of GABAergic function dramatically impact cortical maturation. Based on these data, the traditional view is that the depolarizing action of GABA, a hallmark of immature networks in slice preparations, is at the core of developmental processes. However, in-vivo evidence for such depolarizing role is not clear, raising questions about the contribution of GABAergic neurons in-vivo. To address this issue we developed an in-vivo approach combining optogenetics and single-unit electrophysiology in non-anesthetized mice. This allowed us to both identify and manipulate hippocampal GABAergic cells while examining their influence on hippocampal SNAP. We found that, even during the first post-natal days, the net action of GABA is inhibitory, but not excitatory. This inhibitory action of GABA drastically increases after the second post-natal week.