Pharmacological modulation of contextual "episodic-like" memory in aged mice

Abstract

Episodic memory deficits in elderly are due to the progressive weaknesses to use the contextual and temporal cues of the to be remembered information. Since the inability to remember the specific context of events is an important feature of episodic memory deficits in the elderly, we first focused on describing two mice models of contextual "episodic-like" memory. In a second part, we described the effects of aging on memory in the contextual and serial discrimination (CSD) task. We showed more specifically that the CSD task allowed detection of early memory impairments in middle-aged (14-15 months) animals as compared to young (4-5 months) or aged (18-19 months) ones. Interestingly, the very same memory impairments were observed following dorsal hippocampal lesions in young adult mice, which suggest that the CSD task allowed detection of early signs of age-related hippocampal dysfunction. In a third part, we showed that pharmacological reference compounds such as donepezil and memantine (mainly used in the treatment of mild to severe forms of Alzheimer's diseases) reversed the age-induced memory impairments as well as emerging pharmacological compounds acting on different neurotransmitter targets (nicotinic and AMPA receptors). Thus, the CSD task appears to be a reliable behavioural tool for detecting the early emergence of age-related memory dysfunction and for identifying new pharmacological targets and therapeutic strategies in the treatment of age-related amnesia.