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Neurobiol Aging. 2005 Jan;26(1):53-68.

Spatial memory in aged rats is related to PKCgamma-dependent G-protein coupling of the M1 receptor.

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Department of Neurological Sciences, Rush University Medical Center, Suite 334 Murdoch Building, 1653 West Congress Parkway, Chicago, IL 60612, USA.


In the present study, individual differences in spatial memory in aged Fischer 344 (F344) rats were associated with the extent of G-protein coupling of the M1 muscarinic receptor and the dendritic-to-somal ratio of hippocampal PKCgamma (d/sPKCgamma) immunogenicity. Following testing in the eight-arm radial maze task, 7 young and 13 aged rat brains were sectioned through the dorsal hippocampal formation (HF). G-protein coupling of the M1 receptor was assessed autoradiographically using competition binding studies in the presence and absence of a G-protein uncoupler to determine high (K(H)) and low (K(L)) affinity states for agonist in the HF, neocortex, and amygdala. In aged animals, a relationship between choice accuracy in the maze and K(H), a measure of M1 receptor-G-protein coupling was seen in the dentate gyrus, CA3, CA1, and neocortex. Furthermore, choice accuracy and d/sPKCgamma immunogenicity showed a significant relationship in CA1. Lastly, a correlation was seen in the CA1 of aged animals between K(H) and d/sPKCgamma. These relationships did not hold for the amygdala. Thus, individual differences in a naturally occurring age-dependent disruption of cholinergic-PKCgamma signal transduction is associated with spatial memory dysfunction.

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