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The Journal of Neuroscience, July 25, 2007, 27(30):8046-8052; doi:10.1523/JNEUROSCI.1187-07.2007

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Behavioral/Systems/Cognitive
Mineralocorticoid Receptor Overexpression Differentially Modulates Specific Phases of Spatial and Nonspatial Memory

Deveroux Ferguson¹ and Robert Sapolsky^1,2

¹Department of Biological Sciences, Stanford University, Stanford, California 94305, and ²Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California 94304

Correspondence should be addressed to Deveroux Ferguson, Gilbert Laboratory, Mail Code 5020, Stanford, CA 94305-5020. Email: devero89{at}stanford.edu

Glucocorticoids (GCs) and stress modulate specific phases of information processing. The modulatory affects of GCs on hippocampal function are thought to be mediated by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). The GR plays a critical role in mediating the impairing effects of GCs on hippocampal function. Conversely, activation of MR facilitates hippocampal function. The high affinity of MR for GCs suggests that the receptor protein levels play a key role in regulating the beneficial effects of MR-mediated gene transcription. Using herpes simplex vectors, we transiently increased MR levels in dentate gyrus granule cells, which in turn enhanced MR signaling. We then examined its effects on spatial and nonspatial memory consolidation and retrieval using the object placement and object recognition task. Additionally, we assessed whether an increased MR signal could block the impairing effects of high GCs on memory retrieval. Rats overexpressing MR displayed an enhancement in the consolidation of nonspatial memory relative to rats expressing green fluorescent protein and suggest the potential for gene transfer techniques for enhancing cognition during stress. Moreover, rats overexpressing MR were spared from the disruptive effects of high GCs on the retrieval of nonspatial memory. Thus, this study illustrates the critical role of MR in mediating the retrieval and consolidation of nonspatial memory.

Key words: mineralocorticoid receptor; nonspatial memory; viral vector; spatial memory; corticosterone; learning and memory

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Received Dec. 9, 2006; revised June 18, 2007; accepted June 19, 2007.

Correspondence should be addressed to Deveroux Ferguson, Gilbert Laboratory, Mail Code 5020, Stanford, CA 94305-5020. Email: devero89{at}stanford.edu

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