title: Upstairs/downstairs revisited: spatial pretraining-induced rescue of normal spatial learning during selective blockade of hippocampal N-methyl-d-aspartate receptors.
abstract: Spatial pretraining can enable spatial learning in another environment that ordinarily requires hippocampal N-methyl-d-aspartate (NMDA) receptor activity to become independent of that activity. This study explored further the circumstances in which this training-induced 'rescue' of later learning in the presence of the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (D-AP5) can occur. D-AP5 (0, 10, 20 and 30 mm in artificial cerebrospinal fluid) was infused continuously (0.5 μL/h, from a minipump) and bilaterally into the dorsal hippocampus during spatial-reference-memory training in a watermaze (4 trials/day, 8 days). This was preceded either by handling only or by identical spatial training in another watermaze in a separate laboratory with different extramaze cues. In naïve rats, D-AP5 caused a dose-related impairment in spatial reference memory acquisition that was significant at the lowest 5 nm/h infusion concentration. In pretrained rats, the dose-response function was shifted such that, in watermaze 2, spatial learning was normal at this low concentration, with a deficit at higher infusion concentrations. The induction of long-term potentiation in the dentate gyrus in vivo was blocked at all D-AP5 concentrations. Sensorimotor abnormalities sometimes seen with NMDA receptor antagonists were only apparent at the highest concentration. The implication of this paradoxical dissociation between hippocampal NMDA receptor-dependent plasticity and spatial learning is discussed with reference to two rival hypotheses of the impact of pretraining.
authors.affiliation: Laboratory for Cognitive Neuroscience, Centre for Cognitive and Neural Systems, The University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Inglis
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Martin
authors.forename: Richard G M
authors.initials: RG
authors.lastname: Morris
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D057967:Infusions, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate