Control of food consumption by learned cues: a forebrain-hypothalamic network

Abstract

Motivation plays an important role in the control of food intake. This review will focus on recent findings using a neural systems analysis of a behavioral model for learned motivational control of eating. In this model, environmental cues that acquire motivational properties through Pavlovian conditioning can subsequently override satiety and promote eating in sated rats. Evidence will be presented that a brain network formed by the amygdala, lateral hypothalamus, and medial prefrontal cortex mediates this phenomenon of conditioned potentiation of feeding. The animal model may be informative for understanding control of eating in humans including maladaptive influences that contribute to overeating.

Figure 1

This diagram summarizes recent findings from neural systems analysis of the behavioral model, conditioned potentiation of feeding, that relies on learned cues to override metabolic signals. In that model, a cue previously paired with food when an animal was hungry can initiate eating in sated rats. The lateral hypothalamus (LHA) is an integrative site for feeding signals, both intrinsic and extrinsic. Pathways in red show projections to the LHA with origins in the forebrain neurons that show activation by a conditioned stimulus (CS+) that promotes feeding. The origins of these pathways in the basolateral amygdala (BLA; includes BL, BM, and LA), and ventral medial prefrontal cortex (mPFC; includes PL, ILA, and mOFC) are critical functionally, as shown by lesions of each of these areas, which abolish CS-enhanced feeding. Our studies have further shown that direct projections from CEA are not critical; as indicated by lack of selective activation of that pathway by the effective CS+, and the fact that lesions of CEA spare CS-enhanced feeding. Blue line shows interconnections between the BLA and mPFC that may also play a role in regulation of feeding by learned cues. Abbreviations: ARH, arcuate nucleus of the hypothalamus; BLA, basolateral amygdala; BL, basolateral nucleus of the amygdala; BM, basomedial nucleus of the amygdala; DMH, dorsomedial nucleus of the hypothalamus; ILA, infralimbic area; LA, lateral nucleus of the amygdala; LHA, lateral hypothalamic area; PL, prelimbic area; mOFC, medial orbitofrontal area; VMH, ventromedial nucleus of the hypothalamus. Plates modified from the atlas of Swanson [63].

Figure 2

A population of neurons within the basolateral amygdala (BLA; includes BL, BM, and LA) that project to the medial prefrontal cortex (mPFC) is selectively activated by CS+. A, A photomicrograph of the mPFC in the immunohistochemically-processed tissue after retrograde tracer (FluoroGold, FG) injection. Red line encircles the area of the FG deposit within the mPFC. B, A photomicrograph of the amygdala showing retrogradely labeled neurons (black deposits) within the BLA, after FG injection in the mPFC (shown in A). C, A high power photomicrograph of the BLA. D, A high power photomicrograph showing the region of the BLA demarcated by the red box in C, after combined FG detection with double-label fluorescence in situ hybridization (FISH) for Arc and H1a. Animal injected with FG into the mPFC was tested for food consumption in the presence of CS− and CS+ in two consecutive tests temporally arranged for activation H1a and Arc, respectively. Complete analysis of labeled cells is conducted through the z axis. At the focal plane shown in the figure FG-labeled neurons (green) are also labeled with Arc intranuclear foci, INF, (red, white arrow) activated by CS+, H1a INF (blue) activated by CS− (yellow arrow), or both. Abbreviations: BLA, basolateral amygdala; BL, basolateral nucleus of the amygdala; BM, basomedial nucleus of the amygdala; ILA, infralimbic area; PL, prelimbic area