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Protective cap over CA1 synapses: extrasynaptic glutamate does not reach the postsynaptic density.

Natasha Lozovaya·Sergei Melnik·Timur Tsintsadze·Sergei Grebenyuk·Yuri Kirichok·Oleg Krishtal
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Abstract

Numerous data indicate that nonsynaptic release of glutamate occurs both in normal and pathophysiological conditions. When reaching receptors in the postsynaptic density (PSD), glutamate (Glu) could affect the synaptic transmission. We have tested this possibility in the hippocampal CA1 synapses of rats, either by applying exogenous Glu to the CA1 neurons or by disruption of Glu transporter activity. L-Glu (400 microM) was directly applied to the hippocampal slices acutely isolated from the rats. It produced a strong inhibition of both ortho- and antidromically elicited action potentials fired by CA1 neurons while the excitatory postsynaptic current (EPSC) measured in these neurons remained totally unaffected. The optical isomer D-Glu which is not transported by the systems of Glu uptake inhibited not only orthodromic and antidromic spikes, but also EPSC. Non-specific glutamate transporter inhibitor DL-threo-beta-hydroxyaspartic acid (THA, 400 microM) mimicked the effects of exogenous Glu and produced strong inhibition of both orthodromic and antidromic spikes, without any influence on the amplitude of EPSCs. Dihydrokainate (DHK, 300 microM), selective inhibitor of GLT-1 subtype of glutamate transporter, exerted a significant inhibitory action on the orthodromically evoked spikes and also on the EPSC. Our results indicate that extrasynaptic and PSD membranes of CA1 neurons form separate compartments differing in the mechanisms and efficiency of external Glu processing: the protection of PSD markedly prevails.

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4-AminopyridineAmino Acid Transport System X-AGAnimalsAnimals, NewbornAspartic AcidDizocilpine MaleateDrug InteractionsEvoked PotentialsExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsGlutamic AcidHippocampusIn Vitro TechniquesKainic AcidModels, NeurologicalN-MethylaspartateNeural InhibitionNeuronsPotassium Channel BlockersQuinoxalinesRatsRats, WistarSynapsesComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

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Natasha Lozovaya, Sergei Melnik, Timur Tsintsadze, Sergei Grebenyuk, Yuri Kirichok, Oleg Krishtal. 2004-06-18. Protective cap over CA1 synapses: extrasynaptic glutamate does not reach the postsynaptic density.. https://doi.org/10.1016/j.brainres.2004.03.023

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