TRPM4-dependent post-synaptic depolarization is essential for the induction of NMDA receptor-dependent LTP in CA1 hippocampal neurons

• Verfasst von: Menigoz, Aurélie [VerfasserIn]
• Verfasst von: Ahmed, Tariq [VerfasserIn]
• Verfasst von: Sabanov, Victor [VerfasserIn]
• Verfasst von: Philippaert, Koenraad [VerfasserIn]
• Verfasst von: Pinto, Silvia [VerfasserIn]
• Verfasst von: Kerselaers, Sara [VerfasserIn]
• Verfasst von: Segal, Andrei [VerfasserIn]
• Verfasst von: Freichel, Marc [VerfasserIn]
• Verfasst von: Voets, Thomas [VerfasserIn]
• Verfasst von: Nilius, Bernd [VerfasserIn]
• Verfasst von: Vennekens, Rudi [VerfasserIn]
• Verfasst von: Balschun, Detlef [VerfasserIn]
• Titel: TRPM4-dependent post-synaptic depolarization is essential for the induction of NMDA receptor-dependent LTP in CA1 hippocampal neurons
• Verf.angabe: Aurélie Menigoz, Tariq Ahmed, Victor Sabanov, Koenraad Philippaert, Silvia Pinto, Sara Kerselaers, Andrei Segal, Marc Freichel, Thomas Voets, Bernd Nilius, Rudi Vennekens, Detlef Balschun
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 15 S.
• Fussnoten: Published online: 3 December 2015 ; Gesehen am 05.05.2020
• Titel Quelle: Enthalten in: Pflügers Archiv
• Ort Quelle: Berlin : Springer, 1868
• Jahr Quelle: 2016
• Band/Heft Quelle: 468(2016), 4, Seite 593-607
• ISSN Quelle: 1432-2013
• DOI: doi:10.1007/s00424-015-1764-7
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1697202071

Abstract

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 that TRPM4 is an essential co-activator of N-methyl-d-aspartate (NMDA) receptors (NMDAR) during the induction of long-term potentiation (LTP). Disrupting the Trpm4 gene in mice specifically eliminates NMDAR-dependent LTP, while basal synaptic transmission, short-term plasticity, and NMDAR-dependent long-term depression are unchanged. The induction of LTP in Trpm4−/−neurons was rescued by facilitating NMDA receptor activation or post-synaptic membrane depolarization. Accordingly, we obtained normal LTP in Trpm4−/−neurons in a pairing protocol, where post-synaptic depolarization was applied in parallel to pre-synaptic stimulation. Taken together, our data are consistent with a novel model of LTP induction in CA1 hippocampal neurons, in which TRPM4 is an essential player in a feed-forward loop that generates the post-synaptic membrane depolarization which is necessary to fully activate NMDA receptors during the induction of LTP but which is dispensable for the induction of long-term depression (LTD). These results have important implications for the understanding of the induction process of LTP and the development of nootropic medication.