Contributions of impaired hippocampal plasticity and neurodegeneration to age-related deficits in hormonal pulsatility

Connectivity between the hippocampus and hypothalamus plays an essential role in circadian rhythmicity and stress responsiveness. Both hippocampal dysfunction and loss of hormonal pulsatility have been demonstrated in aged animals, but the possibility of a functional interaction between these two processes remains unexplored. Correlated hippocampal neuropathology and flattening of the circadian rhythms occur in the elderly, and we propose that these processes are causally linked. In this review, we discuss the anatomical and functional nature of hippocampal interconnections with the hypothalamus. We also discuss the results of studies exploring the relationship between circadian phase and hippocampal plasticity in young animals, with the goal of understanding how these mechanisms might be restored in the aging brain.