CA1 synaptic correlates of DG engram reactivation in a mouse model of AD

Stefanie Poll1


Learning induces structural and functional changes in a group of neurons – a so-called engram. This engram becomes partially reactivated upon memory recall and is supposed to encode the memory. Alzheimer's disease (AD) comes along with a severe loss of memories. A previous study showed that stimulation of the engram in the dentate gyrus (DG) is sufficient to induce memory recall and to rescue memory deficits in a mouse model of AD. This suggests that the connectivity of engram cells is intact, yet not strong enough to be activated by natural cues. Thinking of engram stimulation as potential memory rescue strategy, little is known about the effects on downstream regions, like CA1 and whether engram stimulation is sufficient to actively effect afferent post-synapses’ structural plasticity.

We addressed this question by stimulating a contextual engram in DG of mice with AD-like pathology, while monitoring structural plasticity of spines on apical dendrites of CA1 pyramidal neurons. We combined two-photon in vivo microscopy of thy1-YPF x APP/PS1 transgenic mice and activity-dependent DREADD (designer receptors exclusively activated by designer drugs) expression to monitor and manipulate a hippocampus-dependent memory.

Our results support the hypothesis that engram reactivation is sufficient to rescue memory impairments of APP/PS1 mice. Moreover, we provide novel information on the effects of artificial memory recall on the plasticity of neuronal circuits and thus, on its efficiacy. The knowledge about the efficacy and reach of memory manipulation strategies are the basis for accessing its relevance for potential clinical applications.