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Age-related declines in a two-day reference memory task are associated with changes in NMDA receptor subunits in mice.

Magnusson KR, Scruggs B, Zhao X, Hammersmark R - BMC Neurosci (2007)

Bottom Line: NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting.A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing.There was a significant decline in the protein expression of the epsilon2 and zeta1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA. Kathy.Magnusson@oregonstate.edu

ABSTRACT

Background: C57BL/6 mice show a relationship during aging between NMDA receptor expression and spatial reference memory performance in a 12-day task. The present study was designed to determine if age-related deficits could be detected with a shorter testing protocol and whether these deficits showed a relationship with NMDA receptors. Mice were trained in a reference memory task for two days in a Morris water maze. Cued testing was performed either after or prior to reference memory testing. Crude synaptosomes were prepared from prefrontal/frontal cortex and hippocampus of the mice that underwent reference memory testing first. NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting.

Results: Young mice showed significant improvement in probe and place learning when reference memory testing was done prior to cued testing. A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing. There was a significant decline in the protein expression of the epsilon2 and zeta1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex. The subunit changes showed a significant correlation with both place and probe trial performance.

Conclusion: The presence of an age-related decline in performance of the reference memory task regardless of when the cued trials were performed suggests that the deficits were due to factors that were unique to the spatial reference memory task. These results also suggest that declines in specific NMDA receptor subunits in the synaptic pool of prefrontal/frontal brain regions contributed to these age-related problems with performing a spatial reference memory task.

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Diagram of the protocol for reference memory testing over a two day period, including both place learning and probe trials. s, seconds; max., maximum.
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Figure 1: Diagram of the protocol for reference memory testing over a two day period, including both place learning and probe trials. s, seconds; max., maximum.

Mentions: Aged C57BL/6 mice show spatial reference memory problems when tested over 12 days in the Morris water maze [17-19]. We were interested in adopting a task that would show age-related deficits in fewer days in order to test drug interventions with the use of osmotic pumps (Durect Corp., Cupertino, CA). The smallest pump available can deliver drug for 3–14 days, but, in addition to the time necessary for behavioral testing, time is also needed for recovery from surgery and pretraining. Berry and coworkers developed a one-day spatial memory task for rats, in which young rats show good improvement in performance 8 trials in one day [20]. Our initial attempts to use this one-day task with mice showed that young mice could not show a significant improvement within 8 trials in one day, but could with two days of testing (unpublished observation). The present study was designed to determine whether we could detect significant differences in performance between young and old mice in a spatial reference memory task with a two-day testing protocol (Figure 1).


Age-related declines in a two-day reference memory task are associated with changes in NMDA receptor subunits in mice.

Magnusson KR, Scruggs B, Zhao X, Hammersmark R - BMC Neurosci (2007)

Diagram of the protocol for reference memory testing over a two day period, including both place learning and probe trials. s, seconds; max., maximum.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1919384&req=5

Figure 1: Diagram of the protocol for reference memory testing over a two day period, including both place learning and probe trials. s, seconds; max., maximum.
Mentions: Aged C57BL/6 mice show spatial reference memory problems when tested over 12 days in the Morris water maze [17-19]. We were interested in adopting a task that would show age-related deficits in fewer days in order to test drug interventions with the use of osmotic pumps (Durect Corp., Cupertino, CA). The smallest pump available can deliver drug for 3–14 days, but, in addition to the time necessary for behavioral testing, time is also needed for recovery from surgery and pretraining. Berry and coworkers developed a one-day spatial memory task for rats, in which young rats show good improvement in performance 8 trials in one day [20]. Our initial attempts to use this one-day task with mice showed that young mice could not show a significant improvement within 8 trials in one day, but could with two days of testing (unpublished observation). The present study was designed to determine whether we could detect significant differences in performance between young and old mice in a spatial reference memory task with a two-day testing protocol (Figure 1).

Bottom Line: NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting.A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing.There was a significant decline in the protein expression of the epsilon2 and zeta1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA. Kathy.Magnusson@oregonstate.edu

ABSTRACT

Background: C57BL/6 mice show a relationship during aging between NMDA receptor expression and spatial reference memory performance in a 12-day task. The present study was designed to determine if age-related deficits could be detected with a shorter testing protocol and whether these deficits showed a relationship with NMDA receptors. Mice were trained in a reference memory task for two days in a Morris water maze. Cued testing was performed either after or prior to reference memory testing. Crude synaptosomes were prepared from prefrontal/frontal cortex and hippocampus of the mice that underwent reference memory testing first. NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting.

Results: Young mice showed significant improvement in probe and place learning when reference memory testing was done prior to cued testing. A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing. There was a significant decline in the protein expression of the epsilon2 and zeta1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex. The subunit changes showed a significant correlation with both place and probe trial performance.

Conclusion: The presence of an age-related decline in performance of the reference memory task regardless of when the cued trials were performed suggests that the deficits were due to factors that were unique to the spatial reference memory task. These results also suggest that declines in specific NMDA receptor subunits in the synaptic pool of prefrontal/frontal brain regions contributed to these age-related problems with performing a spatial reference memory task.

Show MeSH