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Control and plasticity of the presynaptic action potential waveform at small CNS nerve terminals.

ABSTRACT: The steep dependence of exocytosis on Ca(2+) entry at nerve terminals implies that voltage control of both Ca(2+) channel opening and the driving force for Ca(2+) entry are powerful levers in sculpting synaptic efficacy. Using fast, genetically encoded voltage indicators in dissociated primary neurons, we show that at small nerve terminals K(+) channels constrain the peak voltage of the presynaptic action potential (APSYN) to values much lower than those at cell somas. This key APSYN property additionally shows adaptive plasticity: manipulations that increase presynaptic Ca(2+) channel abundance and release probability result in a commensurate lowering of the APSYN peak and narrowing of the waveform, while manipulations that decrease presynaptic Ca(2+) channel abundance do the opposite. This modulation is eliminated upon blockade of Kv3.1 and Kv1 channels. Our studies thus reveal that adaptive plasticity in the APSYN waveform serves as an important regulator of synaptic function.

SUBMITTER: Hoppa MB

PROVIDER: S-EPMC4283217 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Control and plasticity of the presynaptic action potential waveform at small CNS nerve terminals.

Hoppa Michael B MB Gouzer Geraldine G Armbruster Moritz M Ryan Timothy A TA

Neuron 20141030 4

The steep dependence of exocytosis on Ca(2+) entry at nerve terminals implies that voltage control of both Ca(2+) channel opening and the driving force for Ca(2+) entry are powerful levers in sculpting synaptic efficacy. Using fast, genetically encoded voltage indicators in dissociated primary neurons, we show that at small nerve terminals K(+) channels constrain the peak voltage of the presynaptic action potential (APSYN) to values much lower than those at cell somas. This key APSYN property ad ...[more]

PMID: 25447742

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Project description:BackgroundNerve terminal invasion by an axonal spike activates voltage-gated channels, triggering calcium entry, vesicle fusion, and release of neurotransmitter. Ion channels activated at the terminal shape the presynaptic spike and so regulate the magnitude and duration of calcium entry. Consequently characterization of the functional properties of ion channels at nerve terminals is crucial to understand the regulation of transmitter release. Direct recordings from small neocortical nerve terminals have revealed that external [Ca(2+)] ([Ca(2+)](o)) indirectly regulates a non-selective cation channel (NSCC) in neocortical nerve terminals via an unknown [Ca(2+)](o) sensor. Here, we identify the first component in a presynaptic calcium signaling pathway.Methodology/principal findingsBy combining genetic and pharmacological approaches with direct patch-clamp recordings from small acutely isolated neocortical nerve terminals we identify the extracellular calcium sensor. Our results show that the calcium-sensing receptor (CaSR), a previously identified G-protein coupled receptor that is the mainstay in serum calcium homeostasis, is the extracellular calcium sensor in these acutely dissociated nerve terminals. The NSCC currents from reduced function mutant CaSR mice were less sensitive to changes in [Ca(2+)](o) than wild-type. Calindol, an allosteric CaSR agonist, reduced NSCC currents in direct terminal recordings in a dose-dependent and reversible manner. In contrast, glutamate and GABA did not affect the NSCC currents.Conclusions/significanceOur experiments identify CaSR as the first component in the [Ca(2+)](o) sensor-NSCC signaling pathway in neocortical terminals. Decreases in [Ca(2+)](o) will depress synaptic transmission because of the exquisite sensitivity of transmitter release to [Ca(2+)](o) following its entry via voltage-activated Ca(2+) channels. CaSR may detects such falls in [Ca(2+)](o) and increase action potential duration by increasing NSCC activity, thereby attenuating the impact of decreases in [Ca(2+)](o) on release probability. CaSR is positioned to detect the dynamic changes of [Ca(2+)](o) and provide presynaptic feedback that will alter brain excitability.

Dataset Information

Control and plasticity of the presynaptic action potential waveform at small CNS nerve terminals.

Publications

Control and plasticity of the presynaptic action potential waveform at small CNS nerve terminals.

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