There is now long-lasting evidence that the construction and maturation of cortical networks during
development is activity dependent. In the developing hippocampus, such activity consists of
intermittent busts of activity called early sharp waves (eSPWs) that are spontaneously triggered in the
periphery. With age, eSPWs leave place to a continuous activity regimen dominated by rhythmic
activity. Pioneering ex-vivo experiments suggest that GABAergic interneurons control and
orchestrate immature network activity. In-vivo, however, this role is less clear. While there is evidence
for the recruitment of GABAergic neurons during eSPWs, the precise timing of their activation in
unknown. Furthermore, there are still uncertainties on how GABAergic cells impact the excitability of
the immature hippocampal networks in-vivo. To address these issues, we developed a
combined electrophysiological and optogenetic method allowing us to identify and manipulate
GABAergic neuron activity in neonatal mice. Our results show that GABAergic neurons were more
active than the rest of the recorded population and participated in more eSPWs. We also found
evidence of both spontaneous and GABA-driven inhibition as early as post-natal day (P) 3. This
inhibitory effect increased with age and reached plateau at P9-P10. Putative excitatory effect of
GABAergic firing was negligible. We propose that rather than being caused by a switch in the polarity
of GABA action, such rise of inhibition is due to the rapid growth of peri-somatic GABAergic inputs to
pyramidal cells. The resulting development of feed-back inhibition within hippocampal networks
would allow for the apparition of continuous network dynamics, ultimately supporting the
emergence of cognitive processes.
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