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Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5.
Hippocampus. 1999; 9(2):118-36.H

Abstract

We investigated the role of NMDA receptors in memory encoding and retrieval. A delayed matching-to-place (DMP) paradigm in the watermaze was used to examine 1-trial spatial memory in rats. Over periods of up to 21 days, 4 daily trials were given to an escape platform hidden in a new location each day, with the memory interval (ITI) varying from 15 sec to 2 hours between trials 1 and 2, but always at 15 sec for the remaining ITIs. Using chronic i.c.v. infusions of D-AP5, acute intrahippocampal infusions, ibotenate hippocampus + dentate lesions and relevant aCSF or sham surgery control groups, we established: (1) the DMP task is hippocampal-dependent; (2) D-AP5 causes a delay-dependent impairment of memory in which the Groups x Delay interaction was significant on two separate measures of performance; (3) this memory impairment also occurs with acute intrahippocampal infusions; (4) the impairment occurs irrespective of whether the animals stay in or are removed from the training context during the memory delay interval; and (5) D-AP5 affects neither the retrieval of information about the spatial layout of the environment, nor memory of where the escape platform had been located on the last day before the start of chronic D-AP5 infusion. LTP in vivo in the dentate gyrus was blocked in the chronically-infused D-AP5 rats and HPLC measurements at sacrifice revealed appropriate intrahippocampal levels. Acute intrahippocampal infusion of radiolabelled D-AP5 revealed relatively restricted diffusion and was used to estimate whole-tissue hippocampal drug concentrations. These results indicate that (1) short-term memory for spatial information is independent of NMDA receptors; (2) the rapid consolidation of spatial information into long-term memory requires activation of hippocampal NMDA receptors; (3) NMDA receptors are not involved in memory retrieval; and (4) the delay-related effects of NMDA receptor antagonists on performance of this task cannot be explained in terms of sensorimotor disturbances. The findings relate to the idea that hippocampal synaptic plasticity is involved in event-memory (Morris and Frey, Phil Trans R Soc Lond B 1997;352:1489-1503) and to a computational model of one-trial DMP performance of Foster et al. (unpublished data).

Authors+Show Affiliations

Department and Centre for Neuroscience, University of Edinburgh Medical School, Scotland.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10226773

Citation

Steele, R J., and R G. Morris. "Delay-dependent Impairment of a Matching-to-place Task With Chronic and Intrahippocampal Infusion of the NMDA-antagonist D-AP5." Hippocampus, vol. 9, no. 2, 1999, pp. 118-36.
Steele RJ, Morris RG. Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5. Hippocampus. 1999;9(2):118-36.
Steele, R. J., & Morris, R. G. (1999). Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5. Hippocampus, 9(2), 118-36.
Steele RJ, Morris RG. Delay-dependent Impairment of a Matching-to-place Task With Chronic and Intrahippocampal Infusion of the NMDA-antagonist D-AP5. Hippocampus. 1999;9(2):118-36. PubMed PMID: 10226773.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5. AU - Steele,R J, AU - Morris,R G, PY - 1999/5/5/pubmed PY - 1999/5/5/medline PY - 1999/5/5/entrez SP - 118 EP - 36 JF - Hippocampus JO - Hippocampus VL - 9 IS - 2 N2 - We investigated the role of NMDA receptors in memory encoding and retrieval. A delayed matching-to-place (DMP) paradigm in the watermaze was used to examine 1-trial spatial memory in rats. Over periods of up to 21 days, 4 daily trials were given to an escape platform hidden in a new location each day, with the memory interval (ITI) varying from 15 sec to 2 hours between trials 1 and 2, but always at 15 sec for the remaining ITIs. Using chronic i.c.v. infusions of D-AP5, acute intrahippocampal infusions, ibotenate hippocampus + dentate lesions and relevant aCSF or sham surgery control groups, we established: (1) the DMP task is hippocampal-dependent; (2) D-AP5 causes a delay-dependent impairment of memory in which the Groups x Delay interaction was significant on two separate measures of performance; (3) this memory impairment also occurs with acute intrahippocampal infusions; (4) the impairment occurs irrespective of whether the animals stay in or are removed from the training context during the memory delay interval; and (5) D-AP5 affects neither the retrieval of information about the spatial layout of the environment, nor memory of where the escape platform had been located on the last day before the start of chronic D-AP5 infusion. LTP in vivo in the dentate gyrus was blocked in the chronically-infused D-AP5 rats and HPLC measurements at sacrifice revealed appropriate intrahippocampal levels. Acute intrahippocampal infusion of radiolabelled D-AP5 revealed relatively restricted diffusion and was used to estimate whole-tissue hippocampal drug concentrations. These results indicate that (1) short-term memory for spatial information is independent of NMDA receptors; (2) the rapid consolidation of spatial information into long-term memory requires activation of hippocampal NMDA receptors; (3) NMDA receptors are not involved in memory retrieval; and (4) the delay-related effects of NMDA receptor antagonists on performance of this task cannot be explained in terms of sensorimotor disturbances. The findings relate to the idea that hippocampal synaptic plasticity is involved in event-memory (Morris and Frey, Phil Trans R Soc Lond B 1997;352:1489-1503) and to a computational model of one-trial DMP performance of Foster et al. (unpublished data). SN - 1050-9631 UR - https://www.unboundmedicine.com/medline/citation/10226773/Delay_dependent_impairment_of_a_matching_to_place_task_with_chronic_and_intrahippocampal_infusion_of_the_NMDA_antagonist_D_AP5_ L2 - https://doi.org/10.1002/(SICI)1098-1063(1999)9:2<118::AID-HIPO4>3.0.CO;2-8 DB - PRIME DP - Unbound Medicine ER -