Thrombin regulation of synaptic plasticity: Implications for physiology and pathology

Nicola Maggio*, Zeev Itsekson, Dan Dominissini, Ilan Blatt, Ninette Amariglio, Gideon Rechavi, David Tanne, Joab Chapman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Thrombin, a serine protease involved in the coagulation cascade has been recently shown to affect neuronal function following blood-brain barrier breakdown. Several lines of evidence have shown that thrombin may exist in the brain parenchyma under normal physiological conditions, yet its role in normal brain functions and synaptic transmission has not been established. In an attempt to shed light on the physiological functions of thrombin and Protease Activated Receptor 1 (PAR1) in the brain, we studied the effects of thrombin and a PAR1 agonist on long term potentiation (LTP) in mice hippocampal slices. Surprisingly, different concentrations of thrombin affect LTP through different molecular routes converging on PAR1. High thrombin concentrations induced an NMDA dependent, slow onset LTP, whereas low concentrations of thrombin promoted a VGCCs, mGluR-5 dependent LTP through activated Protein C (aPC). Remarkably, aPC facilitated LTP by activating PAR1 through an Endothelial Protein C Receptor (EPCR)-mediated mechanism which involves intracellular calcium stores. These findings reveal a novel mechanism by which PAR1 may regulate the threshold for synaptic plasticity in the hippocampus and provide additional insights into the role of this receptor in normal and pathological conditions.

Original languageEnglish
Pages (from-to)595-604
Number of pages10
JournalExperimental Neurology
Volume247
DOIs
StatePublished - Sep 2013

Keywords

  • Extracellular proteases
  • Hippocampus
  • LTP
  • PAR1
  • Synaptic plasticity
  • Thrombin

Fingerprint

Dive into the research topics of 'Thrombin regulation of synaptic plasticity: Implications for physiology and pathology'. Together they form a unique fingerprint.

Cite this