Homeostasis Meets Motivation in the Battle to Control Food Intake

Abstract

Signals of energy homeostasis interact closely with neural circuits of motivation to control food intake. An emerging hypothesis is that the transition to maladaptive feeding behavior seen in eating disorders or obesity may arise from dysregulation of these interactions. Focusing on key brain regions involved in the control of food intake (ventral tegmental area, striatum, hypothalamus, and thalamus), we describe how activity of specific cell types embedded within these regions can influence distinct components of motivated feeding behavior. We review how signals of energy homeostasis interact with these regions to influence motivated behavioral output and present evidence that experience-dependent neural adaptations in key feeding circuits may represent cellular correlates of impaired food intake control. Future research into mechanisms that restore the balance of control between signals of homeostasis and motivated feeding behavior may inspire new treatment options for eating disorders and obesity.

Keywords: AGRP; POMC; accumbens; arculate nucleus; dieting; dopamine; ghrelin; glucose; insulin; leptin; orexin; paraventricular thalamic nucleus; reward.

Figure 1.

Major neural nodes controlling food intake. Major neural nodes involved in food intake control are shown in the rodent brain, together with their classically ascribed functions (Anand and Brobeck, 1951; Kelley et al., 2005; Palmiter, 2007; Berridge et al., 2010; Petrovich, 2013). For simplicity, the illustration does not show all interconnections and excludes some additional regions, including components of the MCL (e.g., hippocampus, basolateral amygdala, ventral pallidum) and output pathways. ARC, Arcuate nucleus; PFC, prefrontal cortex; SNc, substantia nigra pars compacta. Image adapted with permission from Franklin and Paxinos (2008).

Figure 2.

Multiple interactions between circuits of homeostasis and motivation. Microcircuitry of major neural nodes involved in food intake control (shown in Fig. 1) are shown in the rodent brain, together with known modulation of specific cell types by signals of energy homeostasis. To emphasize direct and indirect modulation of the MCL by circulating signals of energy homeostasis, only outputs from each region to other key nodes in the MCL are shown. For simplicity, not all known cell types, interconnections, and outputs are shown. ARC, Arcuate nucleus; BLA, basolateral amygdale; CART, cocaine- and amphetamine-regulated transcript; CIN, cholinergic interneuron; GIN, GABAergic interneuron; Glu, glutamate; HIP, hippocampus; MCH, melanin-concentrating hormone; NPY, neuropeptide Y; PFC, prefrontal cortex; VP, ventral pallidum. Images adapted with permission from Franklin and Paxinos (2008).