title: Protease Activated Receptor 2 (PAR2) Induces Long-Term Depression in the Hippocampus through Transient Receptor Potential Vanilloid 4 (TRPV4).
abstract: Protease activated receptors (PARs) are involved in regulating synaptic transmission and plasticity in the brain. While it is well-accepted that PAR1 mediates long-term potentiation (LTP) of excitatory synaptic strength, the role of PAR2 in synaptic plasticity remains not well-understood. In this study, we assessed the role of PAR2-signaling in plasticity at hippocampal Schaffer collateral-CA1 synapses. Using field potential recordings, we report that PAR2-activation leads to long-term depression (LTD) of synaptic transmission through a protein kinase A -dependent, Transient Receptor Potential Vanilloid 4 -mediated mechanism, which requires the activation ofN-methyl-D-aspartate receptors. These results demonstrate that the effects of PAR2 on synaptic plasticity are distinct from what is observed upon PAR1-activation. Thus, we propose that the activation of different classes of PARs, i.e., PAR1 and PAR2, may set the threshold of synaptic plasticity in the hippocampal network by balancing LTP and LTD.
authors.affiliation: Department of Neurology, The Chaim Sheba Medical Center Tel HaShomer, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Shavit-Stein
authors.affiliation: Department of Neurology, The Chaim Sheba Medical Center Tel HaShomer, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Artan-Furman
authors.affiliation: Department of Neurology, The Chaim Sheba Medical Center Tel HaShomer, Israel.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Feingold
authors.affiliation: Department of Neurology, The Chaim Sheba Medical CenterTel HaShomer, Israel; Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel Aviv UniversityTel Aviv, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Ben Shimon
authors.affiliation: Department of Neurology, The Chaim Sheba Medical Center Tel HaShomer, Israel.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Itzekson-Hayosh
authors.affiliation: Department of Neurology, The Chaim Sheba Medical CenterTel HaShomer, Israel; Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel Aviv UniversityTel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv UniversityTel Aviv, Israel.
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
authors.affiliation: Institute of Anatomy II, Faculty of Medicine, Heinrich-Heine-University Duesseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Vlachos
authors.affiliation: Department of Neurology, The Chaim Sheba Medical CenterTel HaShomer, Israel; Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel Aviv UniversityTel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv UniversityTel Aviv, Israel; Talpiot Medical Leadership Program, The Chaim Sheba Medical CenterTel HaShomer, Israel.
authors.forename: Nicola
authors.initials: N
authors.lastname: Maggio
keywords: LTD; PAR2; TRPV4; hippocampus; synaptic plasticity