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 under stood Here we show that sphingosine 1 phosphate (SIP) plays a pivotal role in the formation of memory Addition of SIP to rat hippocampal slices increased the rate of AMPA receptor mediated miniature excitatory postsynaptic cur rents (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 SIP LIP 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 (C) 2010 IBRO Published by Elsevier Ltd All rights reserved