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Published on: August 14, 2015
ATP contributes to the generation of network-driven giant depolarizing potentials in the neonatal rat hippocampus
Victoria F Safiulina1, Alexander M Kasyanov, Elena Sokolova
1Neuroscience Programme, International School for Advanced Studies, Via Beirut 2-4, 34014 Trieste, Italy.
Insights
Adenosine triphosphate (ATP) modulates early hippocampal network activity by influencing giant depolarizing potentials (GDPs) and synaptic events through distinct P2X and P2Y receptors, impacting neuronal excitation during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Neuropharmacology
Background:
- Immature hippocampus exhibits network-driven giant depolarizing potentials (GDPs) reliant on glutamate and GABA.
- Adenosine triphosphate (ATP) is a neurotransmitter with a potential role in early network activity.
Purpose of the Study:
- To investigate the direct contribution of ATP to hippocampal network activity during the first postnatal week.
- To elucidate the specific receptors and mechanisms through which ATP modulates synaptic events.
Main Methods:
- Electrophysiological recordings from CA3 pyramidal cells and interneurons in the immature hippocampus.
- Pharmacological manipulation using receptor antagonists (DPCPX, PPADS) and ectoATPase inhibitors (ARL-67156).
- Assessment of ATP's effects on GDPs, GABAergic spontaneous postsynaptic potentials (GABA-SPSPs), and glutamatergic synaptic activity.
Main Results:
- ATP exhibited a biphasic effect on GDPs (transient facilitation followed by depression) via P2X receptors.
- ATP upregulated GABA-SPSPs on pyramidal cells, indicating a network-driven effect.
- ATP differentially modulated GABAergic (depressed via P2Y1 receptors) and glutamatergic (up/downregulated via P2X receptors) synaptic activity.
Conclusions:
- ATP acts as an excitatory modulator of CA3 pyramidal cells by facilitating GDPs and synaptic potentials.
- Interneurons serve as a common pathway for ATP's excitatory drive propagation.
- ATP, through distinct P2X and P2Y receptors, directly influences hippocampal network activity during early postnatal development.
Abstract:
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.
