ATP contributes to the generation of network-driven giant depolarizing potentials in the neonatal rat hippocampus

In the immature hippocampus, the so-called 'giant depolarizing potentials' (GDPs) are network-driven synaptic events generated by the synergistic action of glutamate and GABA. Here we tested the hypothesis that ATP, a widely distributed neurotransmitter, directly contributes to the network activity during the first postnatal week. We found that in CA3 pyramidal cells, in the presence of the adenosine antagonist 8-cyclopentyl- 1,3-dipropylxanthine (DPCPX), ATP produced a transient facilitation of GDPs; followed by a depressant effect. A similar biphasic effect was produced by blockade of the ectoATPase activity with 6-N,N-diethyl-D-beta,gamma-dibromomethylene ATP (ARL-67156). The effects of exogenous and endogenous ATP on GDPs; were prevented by the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). On pyramidal cells, ATP upregulated spontaneous action-potential-dependent GABA(A)-mediated synaptic events (GABA-SPSPs), suggesting a network-driven effect. Recordings from interneurones allowed comparison of ATP effects on GABAergic and glutamatergic synaptic activity. While ATP depressed GABA-SPSPs via metabotropic P2Y(1) receptors, it up- and downregulated glutamatergic SPSPs via PPADS-sensitive receptors. Thus, ATP exerts an excitatory action on CA3 pyramidal cells via facilitation of GDPs; and SPSPs. This excitatory drive is propagated to pyramidal cells by interneurons that represent the 'common pathway' for generation of GDPs; and SPSPs. Our results show that ATP operating via distinct P2X and P2Y receptors directly contributes to modulate network activity at the early stages of postnatal development.