Suarez AN, Liu CM, Cortella AM, Noble EN, Kanoski SE (2019) Medial septum cholinergic signaling regulates gastrointestinal-derived vagus sensory nerve communication to the hippocampus. Neuroscience 2019 Abstracts 601.19. Society for Neuroscience, Chicago, IL.
Summary: The vagus nerve delivers bi-directional communication between feeding-relevant gastrointestinal (GI) signals and the brain. Vagal sensory-mediated GI satiation signals, including gastric distension and intra-gastric nutrient infusion, activate neurons in the hippocampus (HPC). Recent work from our lab revealed that selective GI-derived vagal sensory signaling is required for HPC-dependent episodic and visuospatial memory, effects accompanied by reduced dorsal HPC (dHPC) expression of neurotrophic and neurogenic markers. To investigate the neural pathways mediating gut regulation of hippocampal-dependent memory, here we investigate the hypothesis that GI-derived signals communicate to dHPC neurons via cholinergic input from the medial septum, a memory-promoting pathway that is vulnerable to disruption in various degenerative dementia diseases. To explore this putative gut-to-brain pathway, we administered 192IgG-saporin, a neurotoxin that selectively kills cholinergic neurons via apoptosis, in the medial septum to determine whether septal cholinergic neurons regulate vagally-mediated neuronal activation in dHPC. Results revealed that elimination of cholinergic neurons in the MS reduced peripherally-administered cholecystokinin (CCK)-induced c-Fos expression in the dHPC, suggesting that cholinergic inputs from the MS transmit GI-derived signaling to the dHPC. Consistent with this interpretation, dHPC protein expression of vesicular acetylcholine transporter (VAChT), which promotes memory function and acetylcholine release without disrupting other co- released molecules, was significantly reduced in rats with GI-specific vagal sensory ablation via nodose ganglion injections of CCK conjugated to saporin. Collectively these results suggest that GI-derived vagal sensory signaling infuences memory function via enhancement of MS cholinergic signaling to the dPHC.