Regulation of synaptic strength by sphingosine 1-phosphate in the hippocampus.
Although the hippocampus is a brain region involved in short-term memory, the molecular mechanisms underlying memory formation are not completely understood. Here we show that sphingosine 1-phosphate (S1P) plays a pivotal role in the formation of memory. Addition of S1P to rat hippocampal slices increased the rate of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) recorded from the CA3 region of the hippocampus. In addition long-term potentiation (LTP) observed in the CA3 region was potently inhibited by a sphingosine kinase (SphK) inhibitor and this inhibition was fully reversed by S1P. LTP was impaired in hippocampal slices specifically in the CA3 region obtained from SphK1-knockout mice, which correlates well with the poor performance of these animals in the Morris water maze test. These results strongly suggest that SphK/S1P receptor signaling plays an important role in excitatory synaptic transmission in the CA3 region of hippocampus and has profound effects on hippocampal function such as spatial learning.
Kanno
T
T
Department of Physiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
Nishizaki
T
T
Proia
R L
RL
Kajimoto
T
T
Jahangeer
S
S
Okada
T
T
Nakamura
S
S
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008246:Lysophospholipids / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014162:Transfection / Q000379:methods; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D000099157:Sphingosine Kinase
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate