Ventro-dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation

• DOI: 10.1016/j.cub.2020.09.074
• Publication Date: 2020-10-15T16:40:01Z
• Authors: Felipe Fredes; Maria Alejandra S...; Peter Koppensteiner; Kenta Kobayashi; Maximilian Joesch; Ryuichi Shigemoto
• Keywords: EXPRESSION; Male; 0301 basic medicine; contextual memory; C-FOS; Mossy Fibers, Hippocampal/diagnostic imaging; Conditioning, Classical; LATENT INHIBITION; Fornix, Brain; Mice, Transgenic; CALRETININ; Memory/physiology; Article; Stereotaxic Techniques; Mice; 03 medical and health sciences; Fornix, Brain/diagnostic imaging; Memory; Neural Pathways; Animals; dentate gyrus; AXIS; mossy cells; GRANULE CELLS; Optical Imaging; Neural Pathways/diagnostic imaging; environmental novelty; HILAR MOSSY CELLS; DENTATE GYRUS; LOCUS-COERULEUS; Models, Animal; Mossy Fibers, Hippocampal; ventral hippocampus; PATTERN SEPARATION

Novelty facilitates memory formation and is detected by both the dorsal and ventral hippocampus. Although dentate granule cells (GCs) in the dorsal hippocampus are known to mediate the formation of novelty-induced contextual memories, the required pathways and mechanisms remain unclear. Here we demonstrate that a powerful excitatory pathway from mossy cells (MCs) in the ventral hippocampus to dorsal GCs is necessary and sufficient for driving dorsal GC activation in novel environment exploration. In vivo Ca2+ imaging in freely moving mice indicated that this pathway relays environmental novelty. Furthermore, manipulation of ventral MC activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MC activity gates contextual memory formation through an intra-hippocampal interaction activated by environmental novelty.