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Differential induction of LTP and LTD is not determined solely by instantaneous calcium concentration: an essential involvement of a temporal factor
Author(s) -
Mizuno Tomoyuki,
Kanazawa Ichiro,
Sakurai Masaki
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01679.x
Subject(s) - long term potentiation , postsynaptic potential , nmda receptor , neuroscience , cnqx , schaffer collateral , chemistry , ltp induction , stimulation , ampa receptor , excitatory postsynaptic potential , synaptic plasticity , long term depression , biophysics , receptor , psychology , biology , biochemistry , inhibitory postsynaptic potential
Two opposite types of synaptic plasticity in the CA1 hippocampus, long‐term potentiation (LTP) and long‐term depression (LTD), require postsynaptic Ca 2+ elevation. To explain these apparently contradictory phenomena, the current view assumes that a moderate postsynaptic increase in Ca 2+ leads to LTD, whereas a large increase leads to LTP. No detailed study has so far been attempted to investigate whether the instantaneous Ca 2+ 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 Mg 2+ ‐free period, as the conditioning stimulus to investigate this. This allowed low‐frequency afferent stimulation to cause a postsynaptic Ca 2+ influx because the voltage‐dependent block of N ‐methyl‐ d ‐aspartate (NMDA) receptor‐channels by Mg 2+ was removed. When delivered during the Mg 2+ ‐free period, a single pulse, as well as 2–600 pulses, induced LTP that was occluded with tetanus‐induced LTP. To decrease the Ca 2+ influx, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors were completely blocked by the addition of 10 µ m 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 Ca 2+ 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 Ca 2+ elevation could be essential factors for differentially inducing LTP or LTD.