A proposed hypothalamic–thalamic–striatal axis for the integration of energy balance, arousal, and food reward

Abstract

We elaborate herein a novel theory of basal ganglia function that accounts for why palatable, energy-dense foods retain high incentive value even when immediate physiological energy requirements have been met. Basal ganglia function has been studied from the perspective of topographical segregation of processing within parallel circuits, with primary focus on motor control and cognition. Recent findings suggest, however, that the striatum can act as an integrated unit to modulate motivational state. We describe evidence that the striatal enkephalin system, which regulates the hedonic impact of preferred foods, undergoes coordinated gene expression changes that track current motivational state with regard to food intake. Striatal enkephalin gene expression is also downregulated by an intrastriatal infusion of a cholinergic muscarinic antagonist, a manipulation that greatly suppresses food intake. To account for these findings, we propose that signaling through a hypothalamic-midline thalamic-striatal axis impinges on the cholinergic interneurons of the striatum, which via their large, overlapping axonal fields act as a network to modulate enkephalin-containing striatal output neurons. A key relay in this circuit is the paraventricular thalamic nucleus, which receives convergent input from orexin-coded hypothalamic energy-sensing and behavioral state-regulating neurons, as well as from circadian oscillators, and projects to cholinergic interneurons throughout the striatal complex. We hypothesize that this system evolved to coordinate feeding and arousal, and to prolong the feeding central motivational state beyond the fulfillment of acute energy needs, thereby promoting "overeating" and the consequent development of an energy reserve for potential future food shortages.

Orexin in Rostral Hotspot of Nucleus Accumbens Enhances Sucrose ‘Liking’ and Intake but Scopolamine in Caudal Shell Shifts ‘Liking’ Toward ‘Disgust’ and ‘Fear’

“…The ability of scopolamine microinjections throughout medial shell to suppress hedonic reactions to sucrose, increase aversive 'disgust' reactions to bitter quinine, and suppress intake of palatable food is consistent with the hypothesis by Kelley et al (2005) that endogenous ACh signals in NAc shell promote food intake (potentially by enhancing palatability). Their ACh-appetite hypothesis arose from the original demonstrations that scopolamine microinjections into NAc suppressed food intake, and that NAc scopolamine microinjections also could serve as an unconditioned stimulus to induce conditioned avoidance of either a paired taste or a paired place (Pratt and Kelley, 2004;Pratt et al, 2007).…”

High-fat diet alters the dopamine and opioid systems: effects across development

“…60 In addition to DA, opioids and the MOR in particular are important in reward of palatable foods. 61,62 Through the work in our laboratory, we were the first to show that consumption of a high-fat diet could downregulate the expression of the MOR within reward circuitry structures. In mice that chronically consume a high-fat diet (from 3 to 20 weeks of age), the MOR expression is decreased within the reward circuitry and unchanged in the hypothalamus.…”

Upregulation of Gene Expression in Reward-Modulatory Striatal Opioid Systems by Sleep Loss

“…A recent study showed that surges of endogenously released striatal ENK act as signals to overeat palatable foods (Difeliceantonio et al, 2012). Accordingly, with regard to food motivation, fluctuations in striatal ENK expression have been hypothesized to track short-term motivational contingencies associated with feeding (Kelley et al, 2005;Will et al, 2007). This model proposes that striatal ENK downregulation is the 'off-switch' that signals recent completion of feeding.…”