Control of non-homeostatic feeding in sated mice using associative learning of contextual food cues

Abstract

Feeding is a complex motivated behavior controlled by a distributed neural network that processes sensory information to generate adaptive behavioral responses. Accordingly, studies using appetitive Pavlovian conditioning confirm that environmental cues that are associated with food availability can induce feeding even in satiated subjects. However, in mice, appetitive conditioning generally requires intensive training and thus can impede molecular studies that often require large numbers of animals. To address this, we developed and validated a simple and rapid context-induced feeding (ctx-IF) task in which cues associated with food availability can later lead to increased food consumption in sated mice. We show that the associated increase in food consumption is driven by both positive and negative reinforcement and that spaced training is more effective than massed training. Ctx-IF can be completed in ~1 week and provides an opportunity to study the molecular mechanisms and circuitry underlying non-homeostatic eating. We have used this paradigm to map brain regions that are activated during Ctx-IF with cFos immunohistochemistry and found that the insular cortex, and other regions, are activated following exposure to cues denoting the availability of food. Finally, we show that inhibition of the insular cortex using GABA agonists impairs performance of the task. Our findings provide a novel assay in mice for defining the functional neuroanatomy of appetitive conditioning and identify specific brain regions that are activated during the development of learned behaviors that impact food consumption.

The physiological control of eating: signals, neurons, and networks

“…More recent work identified a connection between the BLA and the INS as critical for mediating hunger-dependent enhancement of food cue responses. This supports a model whereby the interactions between the BLA and INS can gate appetitive action selection in response to food cues by weighing the predicted interoceptive outcome value with the context of current physiological needs (545,(595)(596)(597)(598).…”

Spaced training enhances equine learning performance

“…Further examination of these studies revealed that two focused on punishment rather than negative reinforcement (Beattie and Corr 2010 ; Wimmer et al 2018 ) and two examined positive rather than negative reinforcement (Amsel et al 1971 ; Marx 1969 ). One study reported that spaced training was more effective than massed training with negative reinforcement in mice (Stern et al 2020 ). Finally, one study included horses (McCall et al 1993 ) trained on an avoidance (Pavlovian) conditioning task.…”

Dissection of insular cortex layer 5 reveals two sublayers with opposing modulatory roles in appetitive behavior

“…The insular cortex (insula) mediates top-down modulation of feeding and drinking behaviors in response to taste quality (1, 2), homeostatic/visceral states (3,4), innate threat (3), and learned stimuli (5)(6)(7)(8)(9)(10), as well as the modulation of emotional (11) and social (3,12,13) behaviors. In particular, the modulation of feeding or drinking is differentially regulated by distinct regions of the insula along the anterior-posterior (A-P) axis (1), and region-specific projections to the amygdala complex are suggested to underlie the behavioral control.…”