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Activation of NMDA receptors is necessary for the induction of associative long‐term potentiation in area CA1 of the rat hippocampal slice
Author(s) -
Murphy K. P. S. J.,
Reid G. P.,
Trentham D. R.,
Bliss T. V. P.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.379be.x
Subject(s) - long term potentiation , nmda receptor , long term depression , chemistry , neuroscience , excitatory postsynaptic potential , ltp induction , 2 amino 5 phosphonovalerate , synapse , glutamate receptor , hippocampal formation , receptor , biophysics , ampa receptor , excitatory amino acid antagonists , biology , biochemistry
1 It is commonly assumed that the role of the strongly activated heterosynaptic input during the induction of associative long‐term potentiation (LTP) is to relieve the magnesium blockade of NMDA receptors located at the weakly stimulated synapses and thereby allow the weak input to undergo potentiation. We tested this assumption by using a caged form of the NMDA receptor antagonist, d ‐(–)‐2‐amino‐5‐phosphonopentanoic acid ( d ‐AP5) to block the activation of NMDA receptors at the weak input in a conditioning protocol for the induction of associative LTP in area CA1 of the rat hippocampal slice. 2 The effect of releasing d ‐AP5 by flash photolysis of 100 μ m caged d ‐AP5 ( N ‐[l‐(2‐nitro‐phenyl)ethoxycarbonyl]‐ d ‐AP5) on pharmacologically isolated NMDA receptor‐mediated field EPSPs was examined in area CA1. The slope of the EPSP was reduced by 71% within 50 ms of the initiation of the photolytic reaction when the concentration of released d ‐AP5 had reached 2.0‐2.5 μ m and was reduced by 95% within 1 min (10 μ m d ‐AP5 released). 3 Associative LTP was induced by pairing a strong tetanus to one input with a weak tetanus (subthreshold for homosynaptic LTP) to a second input. The strong tetanus preceded the weak by 50 ms. Rapid application of d ‐AP5, by flash photolysis of caged d ‐AP5, coincident with the last shock of the strong tetanus, resulted in the blockade of NMDA receptor activation during the period of the weak tetanus. Associative LTP was blocked by photolysis of caged d ‐AP5 but was normally expressed in experiments using caged l ‐AP5. 4 We conclude that activation of NMDA receptors at the weakly activated input is an essential requirement for synaptically induced associative LTP.