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Glutamate is required for depression but not potentiation of long-term presynaptic function.

ABSTRACT: Hebbian plasticity is thought to require glutamate signalling. We show this is not the case for hippocampal presynaptic long-term potentiation (LTP_pre), which is expressed as an increase in transmitter release probability (P_r). We find that LTP_pre can be induced by pairing pre- and postsynaptic spiking in the absence of glutamate signalling. LTP_pre induction involves a non-canonical mechanism of retrograde nitric oxide signalling, which is triggered by Ca²⁺ influx from L-type voltage-gated Ca²⁺ channels, not postsynaptic NMDA receptors (NMDARs), and does not require glutamate release. When glutamate release occurs, it decreases P_r by activating presynaptic NMDARs, and promotes presynaptic long-term depression. Net changes in P_r, therefore, depend on two opposing factors: (1) Hebbian activity, which increases P_r, and (2) glutamate release, which decreases P_r. Accordingly, release failures during Hebbian activity promote LTP_pre induction. Our findings reveal a novel framework of presynaptic plasticity that radically differs from traditional models of postsynaptic plasticity.

SUBMITTER: Padamsey Z

PROVIDER: S-EPMC5714480 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Glutamate is required for depression but not potentiation of long-term presynaptic function.

Padamsey Zahid Z Tong Rudi R Emptage Nigel N

eLife 20171115

Hebbian plasticity is thought to require glutamate signalling. We show this is not the case for hippocampal presynaptic long-term potentiation (LTPpre), which is expressed as an increase in transmitter release probability (Pr). We find that LTPpre can be induced by pairing pre- and postsynaptic spiking in the absence of glutamate signalling. LTPpre induction involves a non-canonical mechanism of retrograde nitric oxide signalling, which is triggered by ...[more]

PMID: 29140248

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Project description:Spike timing-dependent plasticity (STDP) is a Hebbian learning rule important for synaptic refinement during development and for learning and memory in the adult. Given the importance of the hippocampus in memory, surprisingly little is known about the mechanisms and functions of hippocampal STDP. In the present work, we investigated the requirements for induction of hippocampal spike timing-dependent long-term potentiation (t-LTP) and spike timing-dependent long-term depression (t-LTD) and the mechanisms of these 2 forms of plasticity at CA3-CA1 synapses in young (P12-P18) mouse hippocampus. We found that both t-LTP and t-LTD can be induced at hippocampal CA3-CA1 synapses by pairing presynaptic activity with single postsynaptic action potentials at low stimulation frequency (0.2 Hz). Both t-LTP and t-LTD require NMDA-type glutamate receptors for their induction, but the location and properties of these receptors are different: While t-LTP requires postsynaptic ionotropic NMDA receptor function, t-LTD does not, and whereas t-LTP is blocked by antagonists at GluN2A and GluN2B subunit-containing NMDA receptors, t-LTD is blocked by GluN2C or GluN2D subunit-preferring NMDA receptor antagonists. Both t-LTP and t-LTD require postsynaptic Ca(2+) for their induction. Induction of t-LTD also requires metabotropic glutamate receptor activation, phospholipase C activation, postsynaptic IP3 receptor-mediated Ca(2+) release from internal stores, postsynaptic endocannabinoid (eCB) synthesis, activation of CB1 receptors and astrocytic signaling, possibly via release of the gliotransmitter d-serine. We furthermore found that presynaptic calcineurin is required for t-LTD induction. t-LTD is expressed presynaptically as indicated by fluctuation analysis, paired-pulse ratio, and rate of use-dependent depression of postsynaptic NMDA receptor currents by MK801. The results show that CA3-CA1 synapses display both NMDA receptor-dependent t-LTP and t-LTD during development and identify a presynaptic form of hippocampal t-LTD similar to that previously described at neocortical synapses during development.

Dataset Information

Glutamate is required for depression but not potentiation of long-term presynaptic function.

Publications

Glutamate is required for depression but not potentiation of long-term presynaptic function.

Similar Datasets

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