Neural Regulation of Rat Gastric Electrophysiology and Motility: Measurement and Modelling

Rhythmic contractions of the stomach are governed by electrophysiological slow wave activity and modulated by input from neurons. Disorders of gut-brain interaction are a burden on the lives of patients. Electrical stimulation of the vagus nerve modulates gastric motility, and therapeutic applications could be advantageous for patients with drug-refractory disease. However, the mechanisms through which vagus nerve stimulation (VNS) modifies gastric motility need further investigation. This exit seminar presents complementary experimental and computational research into the role of gastric slow waves in the neural regulation of rat gastric motility. Measurement and analysis methods for rat gastric SWs were validated _in vitro_ and _in vivo_ using simultaneous intracellular and extracellular electrical measurements, and videographic recordings. Slow wave activity was characterised in a baseline state, and the effects of three _in vivo_ cervical VNS protocols on slow waves were quantified. A mathematical cell model was formulated to simulate the effect of enteric neural input on gastric electrophysiology and active tension generation. The model predicted that smooth muscle cell sensitivity to intracellular calcium was the major inhibitory mechanism for contraction amplitude. The cell model was embedded in a whole-organ model of rat gastric SW propagation, which was parameterised to model experimentally measured variation in slow wave characteristics. Outcomes from this thesis are a valuable addition to the corpus of gastrointestinal and autonomic neurophysiology research. Experimental methods and outcomes established a baseline for rat gastric slow wave propagation characteristics that will be useful for future investigations. Experimental and modelling results showed that therapeutic cervical VNS treatments may need to be adjusted in a pathology- or patient-specific manner that accounts for the health of the nervous system.