PMID- 19475651 OWN - NLM STAT- MEDLINE DCOM- 20100614 LR - 20131121 IS - 1098-1063 (Electronic) IS - 1050-9631 (Linking) VI - 20 IP - 4 DP - 2010 Apr TI - Modulatory metaplasticity induced by pregnenolone sulfate in the rat hippocampus: a leftward shift in LTP/LTD-frequency curve. PG - 499-512 LID - 10.1002/hipo.20649 [doi] AB - We recently have found that an acute application of the neurosteroid pregnenolone sulfate (PREGS) at 50 muM to rat hippocampal slices induces a long-lasting potentiation (LLP(PREGS)) via a sustained ERK2/CREB activation at perforant-path/granule-cell synapses in the dentate gyrus. This study is a follow up to investigate whether the expression of LLP(PREGS) influences subsequent frequency-dependent synaptic plasticity. Conditioning electric stimuli (CS) at 0.1-200 Hz were given to the perforant-path of rat hippocampal slices expressing LLP(PREGS) to induce long-term potentiation (LTP) and long-term depression (LTD). The largest LTP was induced at about 20 Hz-CS, which is normally a subthreshold frequency, and the largest LTD at 0.5 Hz-CS, resulting in a leftward-shift of the LTP/LTD-frequency curve. Furthermore, the level of LTP at 100 Hz-CS was significantly attenuated to give band-pass filter characteristics of LTP induction with a center frequency of about 20 Hz. The LTP induced by 20 Hz-CS (termed 20 Hz-LTP) was found to be postsynaptic origin and dependent on L-type voltage-gated calcium channel (L-VGCC) but not on N-methyl-D-aspartate receptor (NMDAr). Moreover, the induction of 20 Hz-LTP required a sustained activation of ERK2 that had been triggered by PREGS. In conclusion, the transient elevation of PREGS is suggested to induce a modulatory metaplasticity through a sustained activation of ERK2 in an L-VGCC dependent manner. CI - (c) 2009 Wiley-Liss, Inc. FAU - Chen, Ling AU - Chen L AD - Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, Nanjing, China. lingchen@njmu.edu.cn FAU - Cai, Weiyan AU - Cai W FAU - Chen, Lei AU - Chen L FAU - Zhou, Rong AU - Zhou R FAU - Furuya, Kishio AU - Furuya K FAU - Sokabe, Masahiro AU - Sokabe M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hippocampus JT - Hippocampus JID - 9108167 RN - 0 (Calcium Channels, L-Type) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 73R90F7MQ8 (Pregnenolone) SB - IM MH - Animals MH - Blotting, Western MH - Calcium Channels, L-Type/metabolism MH - Electric Stimulation MH - Hippocampus/*drug effects/physiology MH - Long-Term Potentiation/*drug effects/physiology MH - Long-Term Synaptic Depression/*drug effects/physiology MH - Male MH - Neurons/drug effects/physiology MH - Pregnenolone/*pharmacology MH - Rats MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/metabolism MH - Synapses/drug effects/physiology EDAT- 2009/05/29 09:00 MHDA- 2010/06/15 06:00 CRDT- 2009/05/29 09:00 PHST- 2009/05/29 09:00 [entrez] PHST- 2009/05/29 09:00 [pubmed] PHST- 2010/06/15 06:00 [medline] AID - 10.1002/hipo.20649 [doi] PST - ppublish SO - Hippocampus. 2010 Apr;20(4):499-512. doi: 10.1002/hipo.20649.