Differential induction of LTP and LTD is not determined solely by instantaneous calcium concentration: an essential involvement of a temporal factor

被引:67
作者
Mizuno, T
Kanazawa, I
Sakurai, M [1 ]
机构
[1] Teikyo Univ, Sch Med, Dept Physiol, Tokyo 1738605, Japan
[2] Univ Tokyo, Grad Sch Med, Dept Neurol, Tokyo 1138605, Japan
关键词
hippocampus; low-frequency stimulation; LTD; rat;
D O I
10.1046/j.0953-816x.2001.01679.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Two opposite types of synaptic plasticity in the CA1 hippocampus, long-term potentiation (LTP) and long-term depression (LTD), require postsynaptic Ca2+ elevation. To explain these apparently contradictory phenomena, the current view assumes that a moderate postsynaptic increase in Ca2+ leads to LTD, whereas a large increase leads to LTP. No detailed study has so far been attempted to investigate whether the instantaneous Ca2+ elevation level differentially induces LTP or LTD. We therefore used low-frequency (1 Hz) stimulation of Schaffer collateral/commissural fibers in rat hippocampal slices, during a Mg2+-free period, as the conditioning stimulus to investigate this. This allowed low-frequency afferent stimulation to cause a postsynaptic Ca2+ influx because the voltage-dependent block of N-methyl-D-aspartate (NMDA) receptor-channels by Mg2+ was removed. When delivered during the Mg2+-free period, a single pulse, as well as 2-600 pulses, induced LTP that was occluded with tetanus-induced LTP. To decrease the Ca2+ influx, alpha -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors were completely blocked by the addition of 10 muM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to the conditioning medium, in which 1 Hz afferent stimuli (1-600 pulses) induced less LTP and never induced LTD. To further reduce the Ca2+ influx, NMDA receptors were partially blocked with D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5). A small number of 1 Hz stimuli, however, never induced LTD. Only when the conditioning stimuli exceeded 200 pulses was LTD induced. The present findings provide definitive evidence that protracted conditioning is a prerequisite for the induction of LTD. Thus, not only the amplitude but also the duration of postsynaptic Ca2+ elevation could be essential factors for differentially inducing LTP or LTD.
引用
收藏
页码:701 / 708
页数:8
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