Cholinergic depletion of the medial septum followed by phase shifting does not impair memory or rest–activity rhythms measured under standard light/dark conditions in rats

Abstract

The robustness of an individual's circadian rhythms has been correlated with the quality of their cognitive aging. This has been observed in both human and non-human animals and circadian rhythms are especially disrupted in patients with Alzheimer's disease (AD). It is possible that the circadian disruption observed in AD contributes to the cognitive decline in these patients; however, this has not been conclusively proven. A common observation in AD patients is the loss of basal forebrain cholinergic neurons, some of which project to the suprachiasmatic nucleus (SCN) responsible for maintaining circadian rhythms. We were interested to see if cholinergic depletion increased susceptibility to circadian disruption, and to explore possible interactions between these two factors on measures of learning and memory. We lesioned the cholinergic neurons of the medial septum in rats using the specific immunotoxin 192 IgG Saporin and then disrupted circadian rhythms using a six day phase shifting procedure. We looked at measures of circadian rhythmicity, as well as behaviour on tasks designed to test hippocampal dependent (water maze) or hippocampal independent (fear conditioning) learning and memory. We found no difference between the groups on any of the measures examined suggesting that the cholinergic depletion of the medial septum does not increase susceptibility to circadian disruption, and that this combination of risk factors does not contribute to learning and memory impairments.