Author:

Abstract:

Long-term potentiation (LTP) is an established cellular mechanism of synaptic plasticity that is supposed to occur at synapses during learning. NMDA-receptor mediated LTP is the most common form of LTP in mammalian cortical regions. Very recently, we reported a role for the Transient Receptor Potential channel Melastatin 4 (TRPM4), a Ca2+ activated non-selective cation channel known to be important for Ca2+ dependent changes in membrane potential in several cell types, in hippocampal NMDAR-LTP in vitro (Menigoz et al. 2015). To clarify the role of TRPM4 in hippocampal synaptic plasticity in the intact brain, we recorded LTP in vivo in freely-moving TRPM4 knock-out (KO) and control rats and compared it with further LTP measurements in TRPM4 KO mice in vitro. When LTP was induced by a strong high-frequency stimulation (HFS; 6 trains of 20 bursts at 200 Hz), no difference between TRPM4 KO and control rats was observed. However, when a weaker protocol of 4 trains was applied, an impairment of LTP in TRPM4 KO rats became apparent. Taken together, our in vivo and in vitro data indicate that (i) TRPM4 has a crucial function in the induction of LTP in vitro and in vivo. (ii) When strong inductions protocols are used under in vivo conditions, the contribution of TRPM4 to LTP induction seems to be by-passed by other, not yet known, mechanisms. (iii) Induction of LTP by weaker, ‘more physiological’ protocols requires the activation of TRPM4.