Acute suppression of spontaneous neurotransmission drives synaptic potentiation

Elena Nosyreva, Kristen Szabla, Anita E. Autry-Dixon, Alexey G. Ryazanov, Lisa M. Monteggia, Ege T. Kavalali

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The impact of spontaneous neurotransmission on neuronal plasticity remains poorly understood. Here, we show that acute suppression of spontaneous NMDA receptor-mediated (NMDAR-mediated) neurotransmission potentiates synaptic responses in the CA1 regions of rat and mouse hippocampus. This potentiation requires protein synthesis, brain-derived neurotrophic factor expression, eukaryotic elongation factor-2 kinase function, and increased surface expression of AMPA receptors. Our behavioral studies link this same synaptic signaling pathway to the fast-acting antidepressant responses elicited by ketamine. We also show that selective neurotransmitter depletion from spontaneously recycling vesicles triggers synaptic potentiation via the same pathway asNMDAR blockade, demonstrating that presynaptic impairment of spontaneous release, without manipulation of evoked neurotransmission, is sufficient to elicit postsynaptic plasticity. These findings uncover an unexpectedly dynamic impact of spontaneous glutamate release on synaptic efficacy and provide new insight into a key synaptic substrate for rapid antidepressant action.

Original languageEnglish (US)
Pages (from-to)6990-7002
Number of pages13
JournalJournal of Neuroscience
Volume33
Issue number16
DOIs
StatePublished - Apr 17 2013
Externally publishedYes

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Synaptic Transmission
Antidepressive Agents
Elongation Factor 2 Kinase
Neuronal Plasticity
AMPA Receptors
Synaptic Vesicles
Brain-Derived Neurotrophic Factor
Ketamine
N-Methyl-D-Aspartate Receptors
Neurotransmitter Agents
Glutamic Acid
Hippocampus
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Acute suppression of spontaneous neurotransmission drives synaptic potentiation. / Nosyreva, Elena; Szabla, Kristen; Autry-Dixon, Anita E.; Ryazanov, Alexey G.; Monteggia, Lisa M.; Kavalali, Ege T.

In: Journal of Neuroscience, Vol. 33, No. 16, 17.04.2013, p. 6990-7002.

Research output: Contribution to journalArticle

Nosyreva, E, Szabla, K, Autry-Dixon, AE, Ryazanov, AG, Monteggia, LM & Kavalali, ET 2013, 'Acute suppression of spontaneous neurotransmission drives synaptic potentiation', Journal of Neuroscience, vol. 33, no. 16, pp. 6990-7002. https://doi.org/10.1523/JNEUROSCI.4998-12.2013
Nosyreva, Elena ; Szabla, Kristen ; Autry-Dixon, Anita E. ; Ryazanov, Alexey G. ; Monteggia, Lisa M. ; Kavalali, Ege T. / Acute suppression of spontaneous neurotransmission drives synaptic potentiation. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 16. pp. 6990-7002.
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