Block of theta-burst-induced long-term potentiation by (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid: further evidence against long-term potentiation as a model for learning.
It has been previously reported that block of high-frequency stimulation-induced long-term potentiation of synaptic transmission in the hippocampus does not necessarily lead to impairment of spatial learning. Here we show that (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid, an agonist at group II metabotropic glutamate receptors, completely blocked long-term potentiation induced by a theta-burst type of stimulation protocol (five pulses at 75 Hz per train, 200 ms inter-train interval) in the CA1 region in vivo. The drug did not significantly affect synaptic responses during each train whereas inter-train facilitation of excitatory postsynaptic potentials was slightly reduced. It also produced a large reduction in paired-pulse facilitation (50 ms inter-stimulus interval), possibly indicating that an increase in inhibition might be involved in the block of long-term potentiation. The drug dose used (5 microliters of a 10 mM solution i.c.v.) was half the dose which inhibited high-frequency stimulation-induced long-term potentiation in earlier experiments but which did not prevent learning of spatial tasks. We conclude that long-term potentiation induced by a more physiological stimulation protocol which uses theta-like inter-train intervals does not appear to accurately model the synaptic changes which are believed to occur during learning either.
Hölscher
C
C
Department of Pharmacology and Therapeutics, Trinity College, Dublin, Republic of Ireland.
Anwyl
R
R
Rowan
M J
MJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010507:Periodicity; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018696:Neuroprotective Agents; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane