TRPM4 is a key mediator for NMDA-receptor dependent hippocampal LTP but not LTD
Aurelie
Menigoz1,
Tariq
Ahmed2,
Victor
Sabanov2*,
Kasper
Vinken2,
Silvia
Pinto1,
Sara
Kerselaers1,
Andrei
Segal1,
Marc
Freichel3,
Veit
Flockerzi4,
Bernd
Nilius1,
Thomas
Voets1,
Rudi
D'Hooge2,
Rudi
Vennekens1 and
Detlef
Balschun2
-
1
KU Leuven, Belgium
-
2
KU Leuven, Belgium
-
3
University of Heidelberg, Pharmacological Institute, Germany
-
4
University of Saarland, Experimental and Clinical Pharmakology and Toxikology, Germany
TRPM4 is a calcium-activated but calcium-impermeable non-selective cation (CAN) channel. Previous studies have shown that TRPM4 is an important regulator of Ca2+- dependent changes in membrane potential in excitable and non-excitable cell types. However, its physiological significance in neurons of the central nervous system remained unclear. Here we report that TRPM4 proteins form a CAN channel in CA1 neurons of the hippocampus and we show for the first time an essential role of TRPM4 in the gating mechanism of NMDA-receptors during the induction of LTP. Disrupting the Trpm4 gene in mice specifically eliminates NMDAR-dependent long-term potentiation (LTP) in the hippocampus but basal synaptic transmission, short-term plasticity and NMDAR-dependent long-term depression are unchanged. Whole-cell recordings of CA1 neurons revealed a reduced length of evoked excitatory post-synaptic currents and a reduced neuronal excitability in absence of TRPM4. Importantly, we could isolate a calcium-dependent TRPM4-specific cation current. Based on these data, we postulated an essential function of TRPM4 in the generation of the depolarizing current during LTP induction. Consistent with this hypothesis, we obtained normal LTP when the deficit in intrinsic depolarization in Trpm4-/- neurons was bypassed by a pairing protocol.
Taken together, our data are consistent with a novel model of LTP induction in which TRPM4 is an mandatory player in a feed-forward loop that contributes to the postsynaptic membrane depolarization and is necessary to fully activate NMDA receptors during the induction of LTP while being dispensable during LTD induction.
Keywords:
TRPM4,
LTP,
Hippocampus,
NMDA,
CA1
Conference:
11th National Congress of the Belgian Society for Neuroscience, Mons, Belgium, 22 May - 22 May, 2015.
Presentation Type:
Poster presentation
Topic:
Neuroscience
Citation:
Menigoz
A,
Ahmed
T,
Sabanov
V,
Vinken
K,
Pinto
S,
Kerselaers
S,
Segal
A,
Freichel
M,
Flockerzi
V,
Nilius
B,
Voets
T,
D'Hooge
R,
Vennekens
R and
Balschun
D
(2015). TRPM4 is a key mediator for NMDA-receptor dependent hippocampal LTP but not LTD.
Front. Neurosci.
Conference Abstract:
11th National Congress of the Belgian Society for Neuroscience.
doi: 10.3389/conf.fnins.2015.89.00080
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
30 Apr 2015;
Published Online:
05 May 2015.
*
Correspondence:
Dr. Victor Sabanov, KU Leuven, Leuven, 3000, Belgium, victor.sabanov@ppw.kuleuven.be