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The anticoagulant activated protein C (aPC) promotes metaplasticity in the hippocampus through an EPCR‐PAR1‐S1P1 receptors dependent mechanism
Author(s) -
Maggio Nicola,
Itsekson Zeev,
Ikenberg Benno,
Strehl Andreas,
Vlachos Andreas,
Blatt Ilan,
Tanne David,
Chapman Joab
Publication year - 2014
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.22288
Subject(s) - long term potentiation , chemistry , neuroscience , synaptic plasticity , hippocampus , long term depression , metaplasticity , tetanic stimulation , nmda receptor , hippocampal formation , thrombin , microbiology and biotechnology , receptor , biology , ampa receptor , biochemistry , immunology , platelet
Thrombin and other clotting factors regulate long‐term potentiation (LTP) in the hippocampus through the activation of the protease activated receptor 1 (PAR1) and consequent potentiation of N ‐methyl‐ d ‐aspartate receptor (NMDAR) functions. We have recently shown that the activation of PAR1 either by thrombin or the anticoagulant factor activated protein C (aPC) has differential effects on LTP. While thrombin activation of PAR1 induces an NMDAR‐mediated slow onset LTP, which saturates the ability to induce further LTP in the exposed network, aPC stimulation of PAR1 enhances tetanus induced LTP through a voltage‐gated calcium channels mediated mechanism. In this study, we addressed the mechanisms by which aPC enhances LTP in hippocampal slices. Using extracellular recordings, we show that a short tetanic stimulation, which does not induce LTP, is able to enhance plasticity in the presence of aPC through a mechanism that requires the activation of sphingosine‐1 phosphate receptor 1 and intracellular Ca 2+ stores. These data identify aPC as a “metaplastic molecule”, capable of shifting the threshold of LTP towards further potentiation. Our findings propose novel strategies to enhance plasticity in neurological diseases associated with the breakdown of the blood brain barrier and alterations in synaptic plasticity. © 2014 Wiley Periodicals, Inc.