ePoster

Molecular modulation of PCP signalling modifies pattern separation and completion processes

Eloise Danieland 6 co-authors

Presenting Author

Conference
FENS Forum 2024 (2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Eloise Daniel, Maïté Moreau, Cloé L'Heraux, Noémie Depret, Aline Marighetto, Mireille Montcouquiol, Nathalie Sans

Abstract

Correct memory recall requires two cognitive processes. Pattern separation (PS) is an encoding process that enables the discrimination among similar experiences. Conversely, Pattern completion (PC) allows memory retrieval from partial information. In aging and Alzheimer’s disease (AD), the balance between PS and PC is shifted, in favor of PC over PS, inducing overgeneralization and overlapping memories. Mechanistically, PS and PC rely on the dentate gyrus (DG) and the CA3 hippocampal areas. We previously showed that the DG conditional knock-out of Vangl2 – a core Planar Cell Polarity (PCP) gene – improves the PS and impairs the PC (Robert et al., 2020).Our goal is to use PCP-based molecular tools to modulate the PCP signalling to favor the PS over the PC in adult animals. To bypass the need for Vangl2 deletion and modulate PCP signalling with spatio-temporal resolution, we developed a construct based on a Vangl2 effector. Using viral approaches, we overexpressed the CDaam1 construct in the DG of adult mice, and used an innovating and non-aversive touchscreen-based task to assess the PS. Initial results show an improvement in PS with the CDaam1 construct, that were further validated in the 8-arm radial maze. The mice showed an impairment of PC in the water maze paradigm. These results validate the CDaam1 construct as an effective tool to modulate PS and PC in mice. Our future goal is to use the CDaam1 tool to prevent from cognitive decline in aging and/or AD mice.

Unique ID: fens-24/molecular-modulation-signalling-modifies-30459511