May 17th, 2024 – Mayank Mehta (Center for Physics of Life, UCLA) – Hippocampus 2.0

The hippocampus is implicated in many learning and memory disorders including 
Alzheimer’s. Dozens of drugs have cured these in mice but failed in humans. Hippocampal 
neurons in rodents show robust spatial selectivity. Hence, the standard test of 
hippocampal function in mice is the Morris Water Maze, an allocentric spatial memory 
task. However, hippocampal neurons show very little spatial selectivity in freely 
foraging primates. Could this major difference across species play a role in the lack of 
translation from rodents to primates? Indeed, hippocampal damage in humans causes 
profound non-spatial, egocentric, episodic memory deficits, without any explicit spatial 
component, whose neurophysiological analog in rodents has been unclear. Crucially, the 
mechanisms governing these and a growing diversity of hippocampal responses, e.g. time 
cells, head-direction cells, social cells etc. have remained unclear. We propose a novel 
theory of hippocampal function, Hippocampus 2.0, which can reconcile and explain these 
issues, and provide several experimental validations of this theory. The results provide 
a novel, unified framework and experimental techniques for probing hippocampal function, 
which could improve translation of therapies from mice to humans.

Conference Room R229 – Saint-Germain-des-Prés Campus – 45 rue des Saints-Pères, 75006 Paris – May 17th, 2024 at 11:30 AM