SPARC: Chronic Simultaneous Recording of Gastric Motility and Ad Libitum Feeding Behavior in Awake, Freely Moving Rats with Vagal Nerve Simulation
Authors: Phillips Robert , Tan Zhenjun , Zhang Xueguo , Ward Matthew , Cao Jiayue , Lu Kun-Han , Liu Zhongming , Albors Gabriel , Ganesh Vivek , Sofronici Sydney , Irazoqui Pedro , Rajwa Bartek , Jaffey Deborah , Powley Terry 
Published: April 2020

Objective

In spite of its apparent promise, bioelectric modulation of the vagal innervation of the stomach has had limited success modifying ingestive behavior. But, importantly, stimulation parameters in previous bioelectrical applications were arbitrarily employed without information as to their stimulus‐response relationships or optimal locations. With this in mind, we established a model of chronic vagal nerve stimulation (VNS) where we record GI motility continuously in unanesthetized, freely moving rats while their intake is monitored as they consume chow and water ad libitum (automated food and liquid intake monitors; BioDAQ, Research Diets Inc.).

Methods

A patch electrode (MicroProbes) was attached to the muscle wall of the proximal forestomach of healthy adult male Sprague‐Dawley rats at a site known to contain the highest density of vagal mechanoreceptors. A strain gauge was similarly attached to the muscle wall of the antrum. Rats were maintained in their home cages equipped with BioDAQ feeders, while continuously tethered to overhead commutators. Following recovery, the feeding and drinking behavior as well as antral motility of individual rats was continuously monitored and recorded with and without concomitant VNS (pulse parameters, derived from acute studies: 0.3mA/0.2ms/10Hz; 20s On:40s Off). Subjects were exposed to each of the following four conditions on different days at the onset of lights off: a 2 h fast, a 2 h fast while being stimulated, 2 h ad lib access to chow, and 2 h ad lib access to chow while being stimulated. In a separate study, 2 days of strain gauge activity was continuously recorded: 24 h without stimulation followed by 24 h with stimulation.

Results

Rats recovered quickly following surgery. Compared to the 2 h fasted condition, there was a 17% increase in antral peristalsis (change in amplitude and frequency expressed as area under the curve) when subjects were fasted while being stimulated; similarly, there was an 18% increase in antral peristalsis when subjects were stimulated while consuming chow compared to 2 h intake of chow without stimulation. The same pattern was observed in the 2 d study with a 23% increase in antral activity during 24 h of stimulation compared to 24 h pre‐stimulation. Interestingly, a 12% increase in total chow intake occurred when stimulated for 24 h while no difference was noted in water intake between the two conditions.

Conclusions

Initial exposure to VNS results in a modest increase in antral activity with and without the presence of food in the stomach. Analyses are underway to tease apart the effect of stimulation on motility in relation to meal size. Finally, these findings confirm that our chronic VNS model has considerable potential for determining optimal stimulation parameters necessary for making meaningful changes in gut motility.

Support or Funding Information

SPARC/NIH Office of the Director OT2 OD023847

NIDDK/NIH R01 DK027627