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

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 PKCγ (d/sPKCγ) 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 (KH) and low (KL) affinity states for agonist in the HF, neocortex, and amygdala. In aged animals, a relationship between choice accuracy in the maze and KH, a measure of M1 receptor–G-protein coupling was seen in the dentate gyrus, CA3, CA1, and neocortex. Furthermore, choice accuracy and d/sPKCγ immunogenicity showed a significant relationship in CA1. Lastly, a correlation was seen in the CA1 of aged animals between KH and d/sPKCγ. These relationships did not hold for the amygdala. Thus, individual differences in a naturally occurring age-dependent disruption of cholinergic-PKCγ signal transduction is associated with spatial memory dysfunction.