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- Title
Astrocytic Glutamate Is Not Necessary for the Generation of Epileptiform Neuronal Activity in Hippocampal Slices.
- Authors
Fellin, Tommaso; Gomez-Gonzalo, Marta; Gobbo, Sara; Carmignoto, Giorgio; Haydon, Philip G.
- Abstract
The release of glutamate from astrocytes activates synchronous slow inward currents (SICs) in hippocampal pyramidal neurons, which are mediated by the NMDA receptor and represent a nonsynaptic mechanism to promote the synchronization of neuronal activity. Two recent studies demonstrate that SICs generate neuronal paroxysmal depolarizations resembling those typical of interictal epileptiform activity and proposed that there could be an astrocytic basis of epilepsy (Kang et al., 2005; Tian et al., 2005). We tested this hypothesis using two in vitro models of epileptiform activity in hippocampal slices. Removal of extracellular Mg2+ and application of picrotoxin or perfusion with 0.5 mM Mg2+ and 8.5 mm K+-containing saline result mainly in neuronal ictal- and interictal-like epileptiform activity, respectively. Although both models trigger epileptiform activity, astrocytic Ca²+ oscillations were increased only after slice perfusion with 0 mM Mg2+ and picrotoxin. The activation of astrocytic Ca2+ signaling correlates with an increased frequency of SICs, and, when paired neurons were within 100 µm of one another with synchronous neuronal Ca2+ elevations, the generation of synchronous neuronal depolarizations and action potential discharges. TTX blocked both ictal- and interictal-like epileptiform activity without affecting SICs or SIC-mediated neuronal synchronization. In contrast, NMDA receptor antagonists, which block SICs, did not prevent the generation of either ictal- or interictal-like events. Based on this clear-cut pharmacology, our data demonstrate that nonsynaptic glutamate release from astrocytes is not necessary for the generation of epileptiform activity in vitro, although we cannot exclude the possibility that it may modulate the strength of the ictal (seizure)-like event.
- Publication
Journal of Neuroscience, 2006, Vol 26, Issue 36, p9312
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2836-06.2006