Stratum oriens stimulation-evoked modulation of hippocampal long-term potentiation involves the activation of muscarinic acetylcholine receptors and the inhibition of Kv7/M potassium ion channels.
Acetylcholine is considered to be an endogenous modulator of hippocampal neurotransmission and synaptic plasticity. The activation of muscarinic acetylcholine receptors (mAChRs) reportedly enhances hippocampal synaptic plasticity, which plays an important role in memory function; however, the mechanism by which it enhances synaptic plasticity remains unclear. Here, we examined the involvement of the inhibition of Kv7/M K(+)  channels, which are targets of mAChR modulation, during mAChR activation-induced enhancement of long-term potentiation (LTP) at rat hippocampal Schaffer collateral (SC)-CA1 synapses. When an electrical stimulus was applied to the stratum oriens before tetanic stimulation of the SCs, the magnitude of the induced SC-CA1 synapse LTP was enhanced as compared with that induced without stratum oriens stimulation. In the presence of the mAChR antagonist atropine, tetanic stimulation induced stable LTP, but the stratum oriens stimulation-evoked enhancement of LTP was abolished. The additional application of XE991, a selective blocker of Kv7/M K(+)  channels, rescued the atropine-induced inhibition of LTP enhancement. The phospholipase C (PLC) inhibitor U-73122 inhibited the stratum oriens stimulation-evoked enhancement of LTP. Application of the T/R-type voltage-dependent Ca(2+) channel (VDCC) blocker Ni(2+) abolished the stratum oriens stimulation-evoked enhancement of LTP. In addition, tetanic stimulation with preceding stratum oriens stimulation was able to induce LTP during N-methyl-d-aspartate receptor blockade. We therefore propose that stratum oriens stimulation inhibits Kv7/M K(+)  channels through mAChR activation-induced PLC activation, which leads to VDCC activation, and hence causes sufficient Ca(2+)  influx to enhance LTP.
Department of Psychology, Faculty of Human Sciences, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo 102-8554, Japan.
Etsuko
E
Suzuki
Takashi
T
Okada
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000378:metabolism; D004558:Electric Stimulation; D004963:Estrenes / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D051657:KCNQ1 Potassium Channel / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D020747:Calcium Channels, T-Type; D004963:Estrenes; D051657:KCNQ1 Potassium Channel; D010726:Phosphodiesterase Inhibitors; D026902:Potassium Channel Blockers; D011760:Pyrrolidinones; D011976:Receptors, Muscarinic; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D001285:Atropine; D010738:Type C Phospholipases; D000109:Acetylcholine