Gastric bypass surgery is the most effective treatment for obesity and related comorbidities, with Roux-en-Y gastric bypass (RYGB) being one of the most common procedures. While mechanically restricting the size of the stomach clearly contributes to altered satiety signaling and reduced food intake, several studies have shown that changes in the secretion and actions of gastrointestinal (GI) neurohormones may also play significant roles. Vagally-dependent reflexes are critical to the control, regulation and organization of appropriate GI functions, including early satiety. Visceral sensory information from the GI tract is transduced, encoded and relayed centrally via the afferent vagus nerve, the central terminals of which enter the brainstem via the tractus solitarius and terminate within the nucleus of the tractus solitarius (NTS). NTS neurones integrate this vast volume of sensory information with hormonal and metabolic signals as well as neural inputs from other brainstem and higher central nuclei involved in autonomic homeostasis. The integrated neural response from NTS neurones is then relayed to the adjacent dorsal motor nucleus of the vagus (DMV) which contains the preganglionic parasympathetic motoneurones that supply the motor output to the GI tract via the efferent vagus nerve. Studies from several laboratories have shown that the behavior, responsiveness and activity of vagal sensory neurones is compromised by diet-induced obesity, yet very attention has been paid to the effects of diet or obesity on central brainstem neurones and even less information is available regarding the effects of bariatric surgeries on these neurones. The aim of the present study was to use electrophysiological techniques to determine the effects of diet-induced obesity on the biophysical, morphological and pharmacological properties of vagal efferent motoneurones and whether these effects were reversed by RYGB-induced weight loss. Male Sprague-Dawley rats were fed a high fat diet (HFD; 60%kcal from fat; D12491, Research Diets Inc) from 4 weeks of age for 12 weeks. One group of rats (n=17) underwent RYGB surgery, one group underwent ‘sham’ surgery (n=7) while the remaining rats (n=30) were maintained on high fat diet but did not undergo any surgical intervention. An additional group of rats were fed control diet (13.5%kcal from fat; Purina Mills) from 4 weeks of age for 12-14 weeks (n=19). Whole cell patch clamp recordings were made subsequently from DMV neurones in thin (300um) brainstem slices. There were no differences between HFD and sham surgery rats; these results were therefore grouped. DMV neurones from rats exposed to a HFD for 12-14 weeks were less excitable with a decreased membrane input resistance (290±15MΩ vs 314±22MΩ; P<0.05) and decreased ability to fire action potentials in response to current injection (2.6±0.3 action potentials vs 3.6±0.4 action potentials in response to 30pA current injection; P<0.05 and 4.3±0.4 action potentials vs 5.3±0.6 action potentials in response to 270pA current injection; P<0.05). DMV neurones from HFD rats were also less responsive to superfusion of satiety neuropeptides such as glucagon-like peptide I (GLP-1; 100nM). Specifically, only 3 of 21 HFD neurones tested responded to GLP-1 with an increase in action potential firing, whereas 4 of 7 control neurones tested increased action potential firing in response to GLP-1 (P<0.05). RYGB reversed all of these effects (input resistance 400±37MΩ; P<0.05 vs HFD; P>0.095 vs control; 5.5±0.5 and 9.3±0.7 action potentials in response to 30 and 270pA current injection, respectively, P<0.05 vs HFD and control for both; GLP-1 increased the action potential firing rate of 8 of 10 neurones tested; P<0.05 vs RYGB; P>0.05 vs control) suggesting these effects may be due to obesity, rather than diet. Diet-induced obesity also altered the morphological properties of DMV neurons, increasing the soma size and dendritic arborization, although these morphological alterations were not reversed by RYGB, suggesting these effects may be due to diet, rather than obesity. These studies demonstrate that diet-induced obesity also affects the properties of central autonomic neurons, reducing their excitability and responsiveness to neuropeptides. Furthermore, these results represent the first direct evidence for the plausible effects of RYGB to improve vagal neuronal ‘health’ by reversing some of the effects of a chronic HFD. Vago-vagal neurocircuits appear to remain open to modulation and adaptation throughout life, and understanding the mechanisms of these effects may help in the development of novel therapeutic interventions to alleviate environmental (i.e., dietary) ailments.