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Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation.

ABSTRACT: Action potential-dependent release of synaptic vesicles and short-term synaptic plasticity are dynamically regulated by the endogenous Ca(2+) buffers that shape [Ca(2+)] profiles within a presynaptic bouton. Calmodulin is one of the most abundant presynaptic proteins and it binds Ca(2+) faster than any other characterized endogenous neuronal Ca(2+) buffer. Direct effects of calmodulin on fast presynaptic Ca(2+) dynamics and vesicular release however have not been studied in detail. Using experimentally constrained three-dimensional diffusion modeling of Ca(2+) influx-exocytosis coupling at small excitatory synapses we show that, at physiologically relevant concentrations, Ca(2+) buffering by calmodulin plays a dominant role in inhibiting vesicular release and in modulating short-term synaptic plasticity. We also propose a novel and potentially powerful mechanism for short-term facilitation based on Ca(2+)-dependent dynamic dislocation of calmodulin molecules from the plasma membrane within the active zone.

SUBMITTER: Timofeeva Y

PROVIDER: S-EPMC4486835 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation.

Timofeeva Yulia Y Volynski Kirill E KE

Frontiers in cellular neuroscience 20150701

Action potential-dependent release of synaptic vesicles and short-term synaptic plasticity are dynamically regulated by the endogenous Ca(2+) buffers that shape [Ca(2+)] profiles within a presynaptic bouton. Calmodulin is one of the most abundant presynaptic proteins and it binds Ca(2+) faster than any other characterized endogenous neuronal Ca(2+) buffer. Direct effects of calmodulin on fast presynaptic Ca(2+) dynamics and vesicular release however have not been studied in detail. Using experim ...[more]

PMID: 26190970

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Project description:Astrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which are activated by glutamate along with D-serine or glycine, play a crucial role in learning, memory, and synaptic plasticity. However, the precise impact of astrocyte-released D-serine on neuronal modulation remains insufficiently characterized. To address this, we have used the dominant negative SNARE (dnSNARE) mouse model, which selectively inhibits SNARE-dependent exocytosis from astrocytes. We recorded field excitatory postsynaptic potentials (fEPSPs) in CA3-CA1 synapses within hippocampal slices obtained from dnSNARE mice and wild-type (Wt) littermates. Our results demonstrate that hippocampal θ-burst long-term potentiation (LTP), a critical form of synaptic plasticity, is impaired in hippocampal slices from dnSNARE mice. Notably, this LTP impairment was rescued upon incubation with D-serine. To further investigate the involvement of astrocytes in D-serine-mediated mechanisms of LTP maintenance, we perfused hippocampal slices with L-serine - a substrate used by both neurons and astrocytes for D-serine production. The enhancement in LTP observed in dnSNARE mice was exclusively associated with D-serine presence, with no effects evident in the presence of L-serine. Additionally, both D- and L-serine reduced basal synaptic strength in the hippocampal slices of both Wt and dnSNARE mice. These results provide compelling evidence that distinct processes underlie the modulation of basal synaptic transmission and LTP through D-serine. Our findings underscore the pivotal contribution of astrocytes in D-serine-mediated processes that govern LTP establishment and basal transmission. This study not only provides essential insights into the intricate interplay between neurons and astrocytes but also emphasizes their collective role in shaping hippocampal synaptic function.

Dataset Information

Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation.

Publications

Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation.

Similar Datasets

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