Differential rescue of spatial memory deficits in aged rats by L-type voltage-dependent calcium channel and ryanodine receptor antagonism

•Ryanodine receptor expression is negatively correlated with memory in aged rats.•Antagonism of ryanodine receptors improves spatial memory acquisition in aged rats.•Blocking L-type voltage-dependent Ca+2 channels improves recent memory in aged rats.

Age-associated memory impairments may result as a consequence of neuroinflammatory induction of intracellular calcium (Ca+2) dysregulation. Altered L-type voltage-dependent calcium channel (L-VDCC) and ryanodine receptor (RyR) activity may underlie age-associated learning and memory impairments. Various neuroinflammatory markers are associated with increased activity of both L-VDCCs and RyRs, and increased neuroinflammation is associated with normal aging. In vitro, pharmacological blockade of L-VDCCs and RyRs has been shown to be anti-inflammatory. Here, we examined whether pharmacological blockade of L-VDCCs or RyRs with the drugs nimodipine and dantrolene, respectively, could improve spatial memory and reduce age-associated increases in microglia activation. Dantrolene and nimodipine differentially attenuated age-associated spatial memory deficits but were not anti-inflammatory in vivo. Furthermore, RyR gene expression was inversely correlated with spatial memory, highlighting the central role of Ca+2 dysregulation in age-associated memory deficits.