Post-Ingestion Cues Reinforce Food Seeking Behaviours

Post by Amanda McFarlan 

What's the science?

Feeding behaviours are influenced by many factors, including post-ingestive information about the nutrients in our food. The degree to which these post-ingestive cues mediate food seeking behaviour, however, is not well understood. A growing body of evidence suggests that the gut-brain axis may be involved in communicating information about post-ingestive cues to the brain, however, a direct link between the periphery and the brain has yet to be identified. This week in Neuron, Fernandes and colleagues investigated the mechanisms by which post-ingestive sucrose mediates food seeking behaviours. 

How did they do it?

In the first set of experiments, the authors trained mice to lever press for oral delivery of sucrose or of sucralose (non-caloric artificial sweetener) to determine the effect of sucrose on food seeking behaviours. Since there were significant differences in the response to the two solutions, the authors then surgically implanted a gastric catheter in food and water deprived mice and trained them to lever press for gastric delivery of either sucrose or sucralose to investigate the effect of post-ingestive administration of sucrose on food seeking behaviours. In a different group, mice were given a choice between two levers to press, with each lever resulting in gastric delivery of either sucrose or sucralose. Finally, the authors trained knockout mice that were unable to identify sweet taste to lever press for oral delivery of either sucrose or sucralose to determine whether the activation of oral receptors for sweet taste is necessary for the effects of sucrose on food seeking behaviours. 

To better understand the mechanisms underlying the reinforcing effects of sucrose on food-seeking, the authors used deep-brain calcium imaging to measure the activity of dopaminergic neurons in the ventral tegmental area (VTA) in freely moving mice while they received gastric delivery of either sucrose or sucralose. Next, the authors generated transgenic mice with a modified N-Methyl-D-Aspartate receptor (NDMAR) in dopaminergic neurons to disrupt the activity of these neurons in the VTA. They trained these transgenic mice to lever press for gastric delivery of sucrose or sucralose to determine whether the activity of dopaminergic neurons was necessary for sucrose-mediated food seeking behaviours. Finally, the authors investigated the role of the hepatic vagus nerve (thought to be important for post-ingestive nutrient information) in mediating sucrose-related food seeking behaviours. In addition to testing the effects of hepatic vagus nerve lesions on food seeking behaviours, they used deep-brain calcium imaging to measure the activity of VTA dopaminergic neurons in response to gastric delivery of sucrose or sucralose in mice that were surgically denervated at the hepatic vagus nerve and mice that received a sham surgery. 

What did they find?

The authors found that the number of lever presses was much higher when mice received oral delivery or gastric delivery of a sucrose solution compared to sucralose. They also found that when given the choice, mice consistently pressed the lever that resulted in gastric delivery of sucrose rather than sucralose, which suggests that the feedback from post-ingestive sucrose reinforced food seeking behaviours. Finally, the authors determined that lever pressing in knockout mice that were unable to identify sweet taste was increased for oral delivery of sucrose, but not sucralose, further confirming that the reinforcing effects of sucrose are related to post-ingestive feedback rather than the oral activation of sweet taste receptors.

Next, the authors determined that the activity of dopaminergic neurons in the VTA was increased in mice that received gastric delivery of sucrose, relative to those that received sucralose. Lever pressing did not increase and was similar for gastric delivery of both sucrose and sucralose in transgenic mice with altered NMDARs in VTA dopaminergic neurons. However, mice that received a sham surgery (i.e. hepatic vagus nerve intact) had increased activity in VTA dopaminergic neurons after gastric delivery of sucrose compared to sucralose. Conversely, dopamine neuron activity was not different after gastric delivery of sucrose and sucralose in mice that were surgically denervated at the hepatic vagus nerve. Together, these findings suggest that the activity of VTA dopamine neurons is mediated by the hepatic branch of the vagus nerve and is critical for the reinforcing effects of sucrose in food seeking behaviours. 

What’s the impact?

This is the first study to show that post-ingestive sucrose mediates food seeking behaviours through the modulation of dopaminergic neuron activity in the VTA. The authors also revealed that the activity of the VTA dopaminergic neurons is controlled by the hepatic vagus nerve, which suggests that the gut-brain axis is involved in mediating food seeking behaviours. Together, these findings provide insight into the underlying mechanisms of sucrose-mediated food seeking behaviours that connect the central and peripheral nervous systems. 

Fernandes et al. Postingestive Modulation of Food Seeking Depends on Vagus-Mediated Dopamine Neuron Activity. Neuron (2020). Access the original scientific publication here.