English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Sodium-dependent high-affinity uptake of glutamate is thought to play a major role in the maintenance of very low extracellular concentrations of excitatory amino acids (EAA), and may modulate the actions of released transmitter at G-protein-coupled receptors and extrasynaptic receptors that are activated over a longer distance and time course. We have examined the effects of the recently developed uptake inhibitor L- trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC) on monosynaptically evoked excitatory postsynaptic currents (EPSCs) in very-low-density cultures of hippocampal neurons. L-Trans-PDC produced a decreased amplitude of both the non-NMDA and NMDA receptor-mediated components of monosynaptically evoked EPSCs. Examination of miniature EPSCs (mEPSCs) indicated that changes in the sensitivity of postsynaptic non-NMDA receptors did not underline the decrease in evoked EPSC amplitudes. The metabotropic receptor agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) also depressed both components of the EPSC. The competitive metabotropic receptor antagonist (RS)-alpha- methyl-4-carboxyphenylglycine (MCPG) blocked the depression of EPSC amplitude induced by 1S,3R-ACPD and also blocked the effects of L-trans- PDC. Finally, low concentrations of L-glutamate (2 microM) mimicked the effects of L-trans-PDC on EPSC amplitude. From these results we conclude that the application of L-trans-PDC to cultured hippocampal neurons results in the activation of presynaptic metabotropic receptors, leading to a decrease in synaptic transmission. We propose that this effect is due to an increase in ambient glutamate concentrations following inhibition of glutamate uptake, resulting in presynaptic inhibition of excitatory synaptic transmission.

the journal of neuroscience/the journal of neuroscience

The glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate depresses excitatory synaptic transmission via a presynaptic mechanism in cultured hippocampal neurons