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Postsynaptic calcineurin activity downregulates synaptic transmission by weakening intracellular Ca2+ signaling

J H Wang1, P T Kelly

  • 1Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, Texas 77225, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|June 15, 1997
PubMed

Insights

Calcineurin (CaN) activity in neurons limits synaptic strength. Inhibiting CaN enhances synaptic potentiation by modulating calcium signaling and protein kinase activity, impacting neuronal plasticity.

Area of Science:

  • Neuroscience
  • Cellular signaling
  • Synaptic plasticity

Background:

  • Protein phosphorylation/dephosphorylation are key to neuronal activity and synaptic plasticity.
  • Postsynaptic Ca2+/calmodulin (CaM) signaling pathways influence synaptic strength.
  • Calcineurin (CaN) activity normally limits synaptic responses.

Purpose of the Study:

  • To elucidate the mechanisms by which CaN inhibition leads to synaptic potentiation.
  • To investigate the role of intracellular Ca2+ signaling and downstream kinases in CaN-mediated regulation of synaptic transmission.

Main Methods:

  • Inhibition of postsynaptic CaN activity using FK-506 or an autoinhibitory peptide in hippocampal slices.
  • Co-injection of CaN inhibitors with agents affecting Ca2+ signaling pathways (BAPTA, heparin/dantrolene) or protein kinases (CaM-binding peptide, CaM-KII/PKC pseudosubstrate peptides) into CA1 neurons.
  • Assessment of synaptic potentiation and occlusion of long-term potentiation (LTP).

Main Results:

  • Inhibition of postsynaptic CaN activity by FK-506 or autoinhibitory peptide induced synaptic potentiation, occluding tetanus-induced LTP.
  • This potentiation was observed in adult but not young rats.
  • Co-injection experiments showed that BAPTA, heparin/dantrolene, CaM-binding peptide, or CaM-KII/PKC pseudosubstrate peptides significantly attenuated FK-506-induced synaptic potentiation.

Conclusions:

  • Postsynaptic CaN activity downregulates evoked synaptic transmission.
  • CaN exerts its inhibitory effect by weakening intracellular Ca2+ signals.
  • Downstream protein kinase activities are also modulated by CaN, contributing to the regulation of synaptic strength and plasticity.

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