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Presynaptic modulation of cortical synaptic activity by calcineurin
R G Victor1, G D Thomas, E Marban
1Johns Hopkins University, Division of Cardiology, Baltimore, MD 21205, USA.
Summary
Calcineurin, a phosphatase, regulates neurotransmission. Inhibiting calcineurin (CaN) increases glutamate release from presynaptic terminals in rat cortical neurons, impacting synaptic plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Signaling
Background:
- Synaptic plasticity depends on Ca(2+)-mediated phosphorylation/dephosphorylation.
- Calcineurin (CaN), a Ca(2+)-dependent phosphatase, is implicated in modulating postsynaptic glutamate receptors.
- However, CaN is primarily found in presynaptic fractions in the rat cortex.
Purpose of the Study:
- To investigate whether calcineurin modulates glutamatergic neurotransmission via a presynaptic mechanism.
- To determine the cellular localization and functional role of calcineurin in cortical neurons.
Main Methods:
- Whole-cell patch clamp electrophysiology in fetal rat cortical neurons.
- Application of calcineurin inhibitors cyclosporin A (CsA) and FK506.
- Voltage-clamp recordings of excitatory postsynaptic currents (EPSCs).
Main Results:
- CsA and FK506 significantly increased spontaneous action-potential firing rates.
- CsA enhanced the rate, but not amplitude, of glutamate receptor-mediated EPSCs, indicating increased glutamate release.
- CsA did not affect responses to direct glutamate receptor agonist application, supporting a presynaptic action.
Conclusions:
- Calcineurin plays a presynaptic role in modulating glutamatergic neurotransmission in rat cortical neurons.
- Inhibition of calcineurin enhances glutamate release.
- These findings clarify the presynaptic function of calcineurin in synaptic plasticity.