GABA- and glutamate-mediated network activity in the hippocampus of neonatal and juvenile rats revealed by fast calcium imaging

In the rat hippocampus, during the first postnatal week, network activity i s characterized by GABA-driven giant depolarizing potentials (GDPs) associa ted with calcium signals that are readily blocked when the GABA(A) antagoni st bicuculline is applied to the bath. Towards the end of the first postnat al week, in concomitance with the shift of GABA responses from the depolari zing to the hyperpolarizing direction, functional glutamatergic connections start appearing. At this developmental stage, application of bicuculline b locks GABA(A)-mediated inhibition and induces the appearance of interictal epileptiform discharges. In the present experiments, we have used a high sp atio-temporal resolution imaging system to compare, on a time scale of tens of ms, the onset and propagation of fast calcium transients generated with in a GABAergic or glutamatergic network. We found that, during the first po stnatal week, calcium signals associated to evoked GDPs arise from the acti vation of a local circuitry of neurons spanning the stratum radiatum and th e pyramidal layer. Similar activation patterns were elicited by focal appli cation of GABA in the presence of kynurenic acid, a broad spectrum ionotrop ic glutamatergic antagonist, and were blocked by bicuculline. During the se cond postnatal week, in the presence of bicuculline, calcium signals associ ated with interictal discharges evoked by stimulation of glutamatergic fibr es propagated along the well-defined three-synaptic pathway from the dentat e gyrus to the CA1 hippocampal area. (C) Harcourt Publishers Ltd 2000.