SYNCHRONIZATION OF GABAERGIC INTERNEURONAL NETWORK IN CA3 SUBFIELD OFNEONATAL RAT HIPPOCAMPAL SLICES

1. Cell-attached and whole-cell recordings from interneurons localized in the stratum radiatum of the CA3 subfield (SR-CA3) of neonatal (pos tnatal days 2-5) rat hippocampal slices were performed to study their activity during the generation of GABAergic giant depolarizing potenti als (GDPs) in CA3 pyramidal cells. 2. Dual recordings revealed that du ring the generation of GDPs in CA3 pyramidal cells, the interneurons f ire bursts of spikes, on average 4.5 + 1.4 spikes per burst (cell-atta ched mode). These bursts were induced by periodical large inward curre nts (interneuronal GDPs) recorded in whole-cell mode. 3. Interneuronal GDPs revealed typical features of polysynaptic neuronal network-drive n events: they were blocked by TTX and by high divalent cation medium and they could be evoked in an all-or-none manner by electrical stimul ation in different regions of the hippocampus. The network elements re quired for the generation of GDPs are present in local CA3 circuits si nce spontaneous GDPs were present in the isolated CA3 subfield of the hippocampal slice. 4. Interneuronal GDPs were mediated by GABA(A) and glutamate receptors, since: (i) their reversal potential strongly depe nded on [Cl-](i); (ii) at the reversal potential of GABA(A) postsynapt ic currents an inward component of GDPs was composed of events with th e same kinetics as pha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated EPSCs; and (iii) once GABA(A), receptors mere blocked intracellularly by dialysis with F--MgATP-free solution, the remaining component of interneuronal GDPs reversed near 0 mV and recti fied at membrane potentials more negative than -20 mV, suggesting an i mportant contribution of NMDA receptors in addition to AMPA receptors. 5. In cell-attached recordings from interneurons, electrical stimulat ion in the stratum radiatum evoked a burst of spikes that corresponded to evoked GDPs. Pharmacological study of this response revealed that excitation of SR-CA3 interneurons during GDPs is determined by the co- operative depolarizing actions mediated by GABA and glutamate (AMPA an d NMDA) receptors. Interestingly, after blockade of AMPA receptors, GA BA receptor-mediated depolarization enabled the activation of NMDA rec eptors presumably via attenuation of their voltage-dependent magnesium block. 6. It is concluded that synchronous activation of SR-CA3 inter neurons during generation of GDPs is mediated synaptically and is dete rmined by the co-operation of (i) excitatory GABAergic connections bet ween interneurons and (ii) glutamatergic connections to interneurons o riginating presumably from the pyramidal cells.