Resources
Authors & Affiliations
Harini Srinivasan, Anne Albrecht, Oliver Stork
Abstract
The endogenous circadian rhythm of organisms maintains fundamental physiological processes and behaviour by synchronising them to the external environment. Disturbance to this rhythm in our modern societies, caused by the use of artificial light in dark periods, electronic gadgets, shift work, and poor sleep hygiene negatively impacts physiological and cognitive health. Studies in rodent hippocampus show that neuronal membrane excitability shows a diurnal rhythm and disturbance to the circadian cycle impairs hippocampal plasticity and memory. However, it is not clear how acute circadian disturbance (for example, jet lag) affects hippocampus-dependent memory and the formation of cellular engrams, sparse populations of neurons in different hippocampal substructures including the dentate gyrus (DG) that encode and transiently store memories. In this study, we investigated whether experimental jet lag in mice (6-hour phase delay of the normal light-dark cycle) affects fear memory retrieval and causes impairment to engram formation in the DG. Using intrahippocampal injections of adeno-associated viruses expressing the Robust Activity Marker (RAM), activated engram cells were labelled in adult C57Bl6 male and female mice during a contextual and cued fear-conditioning paradigm. Analysis of training and retrieval-induced neuronal activation with cFos immunohistochemistry revealed a significant reduction in the number of reactivated engram neurons and together with a decreased conditioned freezing behaviour during context-memory retrieval following acute 6h-phase delay, in male but not in female mice. The cellular mechanisms of this regulation, stability of the memory content retrieved and sex differences are currently under investigation. Funded by the German Research Foundation, CRC1436 project A07.