Expression profile of the clustered protocadherins in the mouse hippocampus and their role in engram formation and memory processes — The Association Specialists
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Expression profile of the clustered protocadherins in the mouse hippocampus and their role in engram formation and memory processes (21993)

Olivier Clement 1 , Clara Ortega-de San Luis 2 3 , Charles Herring 1 , Mariia Yurova 2 3 , Esteban Urrieta 2 3 , G Guillaume 2 3 , Lydia Marks 2 3 , Ryan Lister 1 4 , Tomas Ryan 2 3 5 6
  1. Harry Perkins Institute of Medical Research, The University of Western Australia, Nedlands, WA, Australia
  2. School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
  3. Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, Ireland
  4. ARC Centre of Excellence in Plants for Space, The University of Western Australia, Nedlands, WA, Australia
  5. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria
  6. Child & Brian Development Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada

Memories are critical for our survival and are stored in engram cells through plastic changes. Upon memory acquisition, engram cells are thought to refine their synaptic connections to permanently store the newly acquired information. In this process, cell adhesion molecules play a crucial role by mediating precise cell-to-cell interactions and synapse formation. With 57 different genes, the clustered protocadherins (cPcdhs) represent the largest subgroup of the cadherin superfamily of cell surface protein and function as a molecular barcode to mediate highly specific self-recognition, playing a pivotal role in neuronal self-avoidance. If the role of cPcdhs during brain development is well established, their contribution to the regulation of engrams and memory function is poorly understood, which is the focus of this study.

Using single-nucleus sequencing, we first examined the precise expression profile of cPcdhs in engram and non-engram cells in the hippocampus and explored their dynamics during memory processes. Then, using a combination of genetic tools, optogenetics and behavioural tests, we investigated how the manipulation of cPcdhs in the mouse hippocampus alters engram formation and function, leading to memory deficits. Altogether, our results demonstrate the important role for cPcdhs in engram physiology and memory processes.