DEFINITION OF VAGALLY INNERVATED NETWORKS INVOLVED IN HIPPOCAMPAL LEARNING AND MEMORY

Understanding the detailed mechanisms of memory regulation has been at the heart of neuroscience research for many decades. Emerging evidence suggests that fundamental mechanisms beyond the central nervous system, such as gut-brain interactions, can influence hippocampal-dependent memory formation. The vagus nerve allows bidirectional communication between the central nervous system and various organs including the gut. Vagal sensory nerve fibres terminate in the brainstem in the nucleus tractus solitarius (NTS). To better understand the influence of visceral sensory information including potential contributions from the gut microbiome, we are studying neuronal pathways from the NTS to the hippocampus. The medial septum (MS) plays a critical role in the regulation of hippocampal memory dynamics. This project aims to define the previously minimally described NTS-MS-Hippocampus pathway and ultimately how its manipulation can impact hippocampal activity and memory. Here, we focused on anatomical and molecular identification based on combinatorial viral labelling using adeno-associated viruses combined with multi-channel immunohistochemistry. This allowed for specific labelling and identification of NTS neuron subtypes projecting to the MS. Through a transsynaptic approach we further defined MS neurons that directly receive NTS input, including their terminal sites in the hippocampus. These data provide insights into the substrates through which body-brain interactions could influence memory formation.