Modulatory metaplasticity induced by pregnenolone sulfate in the rat hippocampus: a leftward shift in LTP/LTD-frequency curve.
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.
Chen
Ling
L
Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, Nanjing, China. lingchen@njmu.edu.cn
Cai
Weiyan
W
Chen
Lei
L
Zhou
Rong
R
Furuya
Kishio
K
Sokabe
Masahiro
M
D000818:Animals; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011284:Pregnenolone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D020746:Calcium Channels, L-Type; D016194:Receptors, N-Methyl-D-Aspartate; D011284:Pregnenolone