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
相关论文
共 38 条
[1]   DIFFERENT VOLTAGE-DEPENDENT THRESHOLDS FOR INDUCING LONG-TERM DEPRESSION AND LONG-TERM POTENTIATION IN SLICES OF RAT VISUAL-CORTEX [J].
ARTOLA, A ;
BROCHER, S ;
SINGER, W .
NATURE, 1990, 347 (6288) :69-72
[2]  
BARR DS, 1995, J NEUROSCI, V15, P5402
[3]   Long-term depression in hippocampus [J].
Bear, MF ;
Abraham, WC .
ANNUAL REVIEW OF NEUROSCIENCE, 1996, 19 :437-462
[4]   The AM and FM of calcium signalling [J].
Berridge, MJ .
NATURE, 1997, 386 (6627) :759-760
[5]   A SYNAPTIC MODEL OF MEMORY - LONG-TERM POTENTIATION IN THE HIPPOCAMPUS [J].
BLISS, TVP ;
COLLINGRIDGE, GL .
NATURE, 1993, 361 (6407) :31-39
[6]   REGULATION OF HIPPOCAMPAL TRANSMITTER RELEASE DURING DEVELOPMENT AND LONG-TERM POTENTIATION [J].
BOLSHAKOV, VY ;
SIEGELBAUM, SA .
SCIENCE, 1995, 269 (5231) :1730-1734
[7]  
CALABRESI P, 1992, J NEUROSCI, V12, P4224
[8]   MK-801 BLOCKS NMDA RECEPTOR-MEDIATED SYNAPTIC TRANSMISSION AND LONG-TERM POTENTIATION IN RAT HIPPOCAMPAL SLICES [J].
COAN, EJ ;
SAYWOOD, W ;
COLLINGRIDGE, GL .
NEUROSCIENCE LETTERS, 1987, 80 (01) :111-114
[9]   EXCITATORY AMINO-ACIDS IN SYNAPTIC TRANSMISSION IN THE SCHAFFER COLLATERAL COMMISSURAL PATHWAY OF THE RAT HIPPOCAMPUS [J].
COLLINGRIDGE, GL ;
KEHL, SJ ;
MCLENNAN, H .
JOURNAL OF PHYSIOLOGY-LONDON, 1983, 334 (JAN) :33-46
[10]   Ca2+ signaling requirements for long-term depression in the hippocampus [J].
Cummings, JA ;
Mulkey, RM ;
Nicoll, RA ;
Malenka, RC .
NEURON, 1996, 16 (04) :825-833