Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that …

ME Bach, M Barad, H Son, M Zhuo… - Proceedings of the …, 1999 - National Acad Sciences
ME Bach, M Barad, H Son, M Zhuo, YF Lu, R Shih, I Mansuy, RD Hawkins, ER Kandel
Proceedings of the national academy of sciences, 1999National Acad Sciences
To study the physiological and molecular mechanisms of age-related memory loss, we
assessed spatial memory in C57BL/B6 mice from different age cohorts and then measured
in vitro the late phase of hippocampal long-term potentiation (L-LTP). Most young mice
acquired the spatial task, whereas only a minority of aged mice did. Aged mice not only
made significantly more errors but also exhibited greater individual differences. Slices from
the hippocampus of aged mice exhibited significantly reduced L-LTP, and this was …
To study the physiological and molecular mechanisms of age-related memory loss, we assessed spatial memory in C57BL/B6 mice from different age cohorts and then measured in vitro the late phase of hippocampal long-term potentiation (L-LTP). Most young mice acquired the spatial task, whereas only a minority of aged mice did. Aged mice not only made significantly more errors but also exhibited greater individual differences. Slices from the hippocampus of aged mice exhibited significantly reduced L-LTP, and this was significantly and negatively correlated with errors in memory. Because L-LTP depends on cAMP activation, we examined whether drugs that enhanced cAMP would attenuate the L-LTP and memory defects. Both dopamine D1/D5 receptor agonists, which are positively coupled to adenylyl cyclase, and a cAMP phosphodiesterase inhibitor ameliorated the physiological as well as the memory defects, consistent with the idea that a cAMP–protein kinase A-dependent signaling pathway is defective in age-related spatial memory loss.
National Acad Sciences