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In hippocampal CA1 pyramidal neurons, GABAergic synapses are established before glutamatergic synapses. GABAergic interneurons should therefore develop and acquire synapses at an earlier stage to provide the source for GABAergic synapses. We now report that this is indeed the case. At birth and in utero, when nearly all pyramidal neurons are not yet functional, most interneurons have already either GABAergic only or GABAergic and glutamatergic postsynaptic currents. At birth, the morphological maturation of interneurons parallels their individual functional responses. In addition, the formation of functional interneurons types appears to be a sequential process. Interneurons that innervate other interneurons acquire GABA(A) synapses before peridendritic interneurons, but also before perisomatic interneurons that are not yet functional at birth. Therefore, interneurons are the source and the targets of the first synapses formed in the developing circuit. Since GABA was shown to be excitatory in utero, interneurons provide all the excitatory drive at a time when the principal cells are silent. They could therefore play a central role in the formation of the cortical circuit at early developmental stages.

Interneurons are the Source and the Targets of the First Synapses Formed in the Rat Developing Hippocampal Circuit