Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5 - PubMed (original) (raw)
Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5
R J Steele et al. Hippocampus. 1999.
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).
Comment in
- Progress in spanning the molecular and behavioral mechanisms of hippocampal function.
Eichenbaum H. Eichenbaum H. Hippocampus. 1999;9(2):100. doi: 10.1002/(SICI)1098-1063(1999)9:2<100::AID-HIPO2>3.0.CO;2-P. Hippocampus. 1999. PMID: 10226771 No abstract available.
Similar articles
- Distinct components of spatial learning revealed by prior training and NMDA receptor blockade.
Bannerman DM, Good MA, Butcher SP, Ramsay M, Morris RG. Bannerman DM, et al. Nature. 1995 Nov 9;378(6553):182-6. doi: 10.1038/378182a0. Nature. 1995. PMID: 7477320 - 5-HT(1A) and NMDA receptors interact in the rat medial septum and modulate hippocampal-dependent spatial learning.
Elvander-Tottie E, Eriksson TM, Sandin J, Ogren SO. Elvander-Tottie E, et al. Hippocampus. 2009 Dec;19(12):1187-98. doi: 10.1002/hipo.20596. Hippocampus. 2009. PMID: 19309036 - Hippocampal synaptic plasticity and NMDA receptors: a role in information storage?
Morris RG, Davis S, Butcher SP. Morris RG, et al. Philos Trans R Soc Lond B Biol Sci. 1990 Aug 29;329(1253):187-204. doi: 10.1098/rstb.1990.0164. Philos Trans R Soc Lond B Biol Sci. 1990. PMID: 1978364 Review. - Hippocampal synaptic plasticity: role in spatial learning or the automatic recording of attended experience?
Morris RG, Frey U. Morris RG, et al. Philos Trans R Soc Lond B Biol Sci. 1997 Oct 29;352(1360):1489-503. doi: 10.1098/rstb.1997.0136. Philos Trans R Soc Lond B Biol Sci. 1997. PMID: 9368938 Free PMC article. Review.
Cited by
- Synaptic rearrangement of NMDA receptors controls memory engram formation and malleability in the cortex.
Bessières B, Dupuis J, Groc L, Bontempi B, Nicole O. Bessières B, et al. Sci Adv. 2024 Aug 30;10(35):eado1148. doi: 10.1126/sciadv.ado1148. Epub 2024 Aug 30. Sci Adv. 2024. PMID: 39213354 Free PMC article. - Use of Ordered Beta Regression Unveils Cognitive Flexibility Index and Longitudinal Cognitive Training Signatures in Normal and Alzheimer's Disease Pathological Aging.
Alveal-Mellado D, Giménez-Llort L. Alveal-Mellado D, et al. Brain Sci. 2024 May 15;14(5):501. doi: 10.3390/brainsci14050501. Brain Sci. 2024. PMID: 38790478 Free PMC article. - Behavioral Analysis of NMDAR Function in Rodents: Tests of Long-Term Spatial Memory.
Bannerman DM, Barkus C, Eltokhi A. Bannerman DM, et al. Methods Mol Biol. 2024;2799:107-138. doi: 10.1007/978-1-0716-3830-9_7. Methods Mol Biol. 2024. PMID: 38727905 - Rodent maze studies: from following simple rules to complex map learning.
Wijnen K, Genzel L, van der Meij J. Wijnen K, et al. Brain Struct Funct. 2024 May;229(4):823-841. doi: 10.1007/s00429-024-02771-x. Epub 2024 Mar 15. Brain Struct Funct. 2024. PMID: 38488865 Free PMC article. Review. - Sharpening the blades of the dentate gyrus: how adult-born neurons differentially modulate diverse aspects of hippocampal learning and memory.
Berdugo-Vega G, Dhingra S, Calegari F. Berdugo-Vega G, et al. EMBO J. 2023 Nov 15;42(22):e113524. doi: 10.15252/embj.2023113524. Epub 2023 Sep 25. EMBO J. 2023. PMID: 37743770 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources