Research Mentor(s)

Mike Mana

Affiliated Department

Brain-Behavioral Neuroscience

Sort Order

14

Start Date

14-5-2015 10:00 AM

End Date

14-5-2015 2:00 PM

Keywords

NMDA, Cognition, Prefrontal cortex, Memory

Document Type

Event

Abstract

Dysfunction of glutamate NMDA receptors may contribute to cognitive deficits in schizophrenia. In the present study, we examined the effects of chronic NMDA receptor dysfunction in the ventral medial prefrontal cortex (mPFC) on the acquisition of a spatial reference memory (SRM) and spatial working memory (SWM) radial maze task as employed by Niewoehner et al (2007). Localized NR1 gene deletions were induced in the ventral mPFC of floxed NR1 mice (DEL, n=10) using an AAV-Cre vector; control mice (CON, n=10) received sham deletions. In the SRM task, food was placed in 3 of 6 arms of an automated radial maze at the start of each trial. Mice were placed in the central chamber of the maze and allowed to enter any arm before returning to the center for a 10-s timeout. Only the previously unchosen arms were then made accessible. This sequence was continued until the mouse had entered all 3 baited arms or the trial was terminated (6 min). Thus, this phase of the task only assessed SRM errors, or entries to arms that were never baited. Following acquisition of the SRM task, a spatial working memory (SWM) component was added. During this phase mice were no longer prevented from re-entering a previously chosen arm. Re-entries were recorded as SWM errors. Performance was also assessed under conditions of a 5-s and 30-s timeout as well as rotation of the maze. NMDA receptor dysfunction in the ventral mPFC had no effect on acquisition of the SRM task or performance in the SWM component. Whereas reducing the timeout from 10-s to 5-s did not significantly alter SRM or SWM performance of either group, performance of both control and deleted mice was significantly impaired when the delay was extended from to 30-s or the maze was rotated to dissociate baited arms from the spatial cues. The most robust performance deficits were observed in response to the maze rotation, which increased SRM and SWM errors. This effect was potentiated in deleted mice where there was a tendency for deleted mice to exhibit a greater number of SWM errors than controls (4.0±1.1 and 2.8±0.8, respectively). These results suggest performance deficits associated with PFC NMDA receptor dysfunction reflect impairment of the ability to modify behavior in the presence of changes in the environment.

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Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this documentation for commercial purposes, or for financial gain, shall not be allowed without the author's written permission.

Language

English

Format

application/pdf

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May 14th, 10:00 AM May 14th, 2:00 PM

Effects of medial prefrontal cortex NMDA NR-1 subunit deletion in adult mice on spatial reference and working memory

Brain-Behavioral Neuroscience

Dysfunction of glutamate NMDA receptors may contribute to cognitive deficits in schizophrenia. In the present study, we examined the effects of chronic NMDA receptor dysfunction in the ventral medial prefrontal cortex (mPFC) on the acquisition of a spatial reference memory (SRM) and spatial working memory (SWM) radial maze task as employed by Niewoehner et al (2007). Localized NR1 gene deletions were induced in the ventral mPFC of floxed NR1 mice (DEL, n=10) using an AAV-Cre vector; control mice (CON, n=10) received sham deletions. In the SRM task, food was placed in 3 of 6 arms of an automated radial maze at the start of each trial. Mice were placed in the central chamber of the maze and allowed to enter any arm before returning to the center for a 10-s timeout. Only the previously unchosen arms were then made accessible. This sequence was continued until the mouse had entered all 3 baited arms or the trial was terminated (6 min). Thus, this phase of the task only assessed SRM errors, or entries to arms that were never baited. Following acquisition of the SRM task, a spatial working memory (SWM) component was added. During this phase mice were no longer prevented from re-entering a previously chosen arm. Re-entries were recorded as SWM errors. Performance was also assessed under conditions of a 5-s and 30-s timeout as well as rotation of the maze. NMDA receptor dysfunction in the ventral mPFC had no effect on acquisition of the SRM task or performance in the SWM component. Whereas reducing the timeout from 10-s to 5-s did not significantly alter SRM or SWM performance of either group, performance of both control and deleted mice was significantly impaired when the delay was extended from to 30-s or the maze was rotated to dissociate baited arms from the spatial cues. The most robust performance deficits were observed in response to the maze rotation, which increased SRM and SWM errors. This effect was potentiated in deleted mice where there was a tendency for deleted mice to exhibit a greater number of SWM errors than controls (4.0±1.1 and 2.8±0.8, respectively). These results suggest performance deficits associated with PFC NMDA receptor dysfunction reflect impairment of the ability to modify behavior in the presence of changes in the environment.

 

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