TRPM4-dependent post-synaptic depolarization is essential for the induction of NMDA receptor-dependent LTP in CA1 hippocampal neurons. 2016

Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, University of Leuven, Herestraat 49, bus 802, 3000, Leuven, Belgium.

TRPM4 is a calcium-activated but calcium-impermeable non-selective cation (CAN) channel. Previous studies have shown that TRPM4 is an important regulator of Ca(2+)-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.

UI MeSH Term Description Entries
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016194 Receptors, N-Methyl-D-Aspartate A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity. N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D017774 Long-Term Potentiation A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. Long Term Potentiation,Long-Term Potentiations,Potentiation, Long-Term,Potentiations, Long-Term
D050053 TRPM Cation Channels A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes. TRPM Cation Channel,Transient Receptor Potential Channels, Type M,Cation Channel, TRPM,Cation Channels, TRPM,Channel, TRPM Cation,Channels, TRPM Cation
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055366 Synaptic Potentials The voltages across pre- or post-SYNAPTIC MEMBRANES. Postsynaptic Current,Postsynaptic Potentials,Synaptic Potential,Current, Postsynaptic,Currents, Postsynaptic,Postsynaptic Currents,Postsynaptic Potential,Potential, Postsynaptic,Potential, Synaptic,Potentials, Postsynaptic
D056547 CA1 Region, Hippocampal One of four subsections of the hippocampus described by Lorente de No, located furthest from the DENTATE GYRUS. CA1 Field of Hippocampus,CA1 Pyramidal Cell Area,CA1 Pyramidal Cell Layer,CA1 Stratum Pyramidale,CA1 Stratum Radiatum,Cornu Ammonis 1 Area,Hippocampal Sector CA1,Hippocampus CA1 Field,Regio Superior of Hippocampus,Stratum Radiatum, CA1,CA1 Field, Hippocampus,CA1 Stratum Radiatums,CA1, Hippocampal Sector,Field, Hippocampus CA1,Hippocampal CA1 Region,Hippocampus Regio Superior,Radiatum, CA1 Stratum,Radiatums, CA1 Stratum,Region, Hippocampal CA1,Sector CA1, Hippocampal,Stratum Pyramidale, CA1,Stratum Radiatums, CA1
D025461 Feedback, Physiological A mechanism of communication with a physiological system for homeostasis, adaptation, etc. Physiological feedback is mediated through extensive feedback mechanisms that use physiological cues as feedback loop signals to control other systems. Feedback, Biochemical,Feedback Inhibition, Biochemical,Feedback Regulation, Biochemical,Feedback Stimulation, Biochemical,Negative Feedback, Biochemical,Positive Feedback, Biochemical,Biochemical Feedback,Biochemical Feedback Inhibition,Biochemical Feedback Inhibitions,Biochemical Feedback Regulation,Biochemical Feedback Regulations,Biochemical Feedback Stimulation,Biochemical Feedback Stimulations,Biochemical Feedbacks,Biochemical Negative Feedback,Biochemical Negative Feedbacks,Biochemical Positive Feedback,Biochemical Positive Feedbacks,Feedback Inhibitions, Biochemical,Feedback Regulations, Biochemical,Feedback Stimulations, Biochemical,Feedback, Biochemical Negative,Feedback, Biochemical Positive,Feedbacks, Biochemical,Feedbacks, Biochemical Negative,Feedbacks, Biochemical Positive,Feedbacks, Physiological,Inhibition, Biochemical Feedback,Inhibitions, Biochemical Feedback,Negative Feedbacks, Biochemical,Physiological Feedback,Physiological Feedbacks,Positive Feedbacks, Biochemical,Regulation, Biochemical Feedback,Regulations, Biochemical Feedback,Stimulation, Biochemical Feedback,Stimulations, Biochemical Feedback

Related Publications

Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
May 2004, Journal of neurophysiology,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
December 1996, Cell,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
March 1994, Journal of neurophysiology,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
November 1993, Journal of neurophysiology,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
March 1997, Brain research,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
October 2013, Physiological reports,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
January 2020, Brain and neuroscience advances,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
January 2015, eNeuro,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
June 2017, Scientific reports,
Aurélie Menigoz, and Tariq Ahmed, and Victor Sabanov, and Koenraad Philippaert, and Silvia Pinto, and Sara Kerselaers, and Andrei Segal, and Marc Freichel, and Thomas Voets, and Bernd Nilius, and Rudi Vennekens, and Detlef Balschun
August 2003, Neuroscience research,
Copied contents to your clipboard!