Upstairs/downstairs revisited: spatial pretraining-induced rescue of normal spatial learning during selective blockade of hippocampal N-methyl-d-aspartate receptors

Jennifer Inglis, Stephen J. Martin, Richard G. M. Morris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 30mm in artificial cerebrospinal fluid) was infused continuously (0.5L/h, from a minipump) and bilaterally into the dorsal hippocampus during spatial-reference-memory training in a watermaze (4trials/day, 8days). This was preceded either by handling only or by identical spatial training in another watermaze in a separate laboratory with different extramaze cues. In naive rats, D-AP5 caused a dose-related impairment in spatial reference memory acquisition that was significant at the lowest 5nm/h infusion concentration. In pretrained rats, the doseresponse 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.

Original languageEnglish
Pages (from-to)718-727
Number of pages10
JournalEuropean Journal of Neuroscience
Volume37
Issue number5
DOIs
Publication statusPublished - Mar 2013

Keywords / Materials (for Non-textual outputs)

  • LONG-TERM POTENTIATION
  • DEFICITS
  • DETAILED BEHAVIORAL-ANALYSIS
  • glutamate receptors
  • WATER MAZE ACQUISITION
  • spatial learning
  • INTRAHIPPOCAMPAL INFUSION
  • SYNAPTIC PLASTICITY
  • watermaze
  • NMDA RECEPTORS
  • MEMORY
  • ANTAGONIST
  • pretraining
  • DORSAL HIPPOCAMPUS
  • cognitive map
  • long-term potentiation

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