Higher-Order Inputs Involved in Appetite Control

Abstract

The understanding of the neural control of appetite sheds light on the pathogenesis of eating disorders such as anorexia nervosa and obesity. Both diseases are a result of maladaptive eating behaviors (overeating or undereating) and are associated with life-threatening health problems. The fine regulation of appetite involves genetic, physiological, and environmental factors, which are detected and integrated in the brain by specific neuronal populations. For centuries, the hypothalamus has been the center of attention in the scientific community as a key regulator of appetite. The hypothalamus receives and sends axonal projections to several other brain regions that are important for the integration of sensory and emotional information. These connections ensure that appropriate behavioral decisions are made depending on the individual's emotional state and environment. Thus, the mechanisms by which higher-order brain regions integrate exteroceptive information to coordinate feeding is of great importance. In this review, we will focus on the functional and anatomical projections connecting the hypothalamus to the limbic system and higher-order brain centers in the cortex. We will also address the mechanisms by which specific neuronal populations located in higher-order centers regulate appetite and how maladaptive eating behaviors might arise from altered connections among cortical and subcortical areas with the hypothalamus.

Keywords: Appetite; Cortex; Eating disorders; Hypothalamus; Obesity; Subcortical areas.

Fig 1.. Cortical and Subcortical connections to Hypothalamus.

Efferent and afferent projections from the hypothalamus to many cortical and subcortical structures are summarized in this figure. Many of these projections are important in the regulation of hypothalamic activity and appetite control. OFC: orbitofrontal cortex; IC: insular cortex: HPC: hippocampus, HY: hypothalamus, PFC: prefrontal cortex, ACC: anterior cingulate cortex; LS: lateral septum; BNST: bed nucleus of stria terminalis; Amy: Amygdala.

Fig 2.. Coordination of eating behavior by multiple brain regions.

Together with the hypothalamus, the insular cortex and other brain regions receive interoceptive information from peripheral organs. This information is processed along with environmental, sensory and emotional information by other cortical and subcortical areas, ultimately leading to changes in food intake. The hypothalamus ultimately projects to midbrain and brainstem areas controlling behavior (VTA: ventral tegmental area; PBN: parabrachial nucleus; PAG: periaqueductal gray; NTS: nucleus tractus solitarius). Many of the cortical (ACC: anterior cingulate cortex, PFC: prefrontal cortex, OFC: orbitofrontal cortex, IC: insular cortex) and subcortical (HPC: hippocampus, LS: lateral septum, BNST: bed nucleus of stria terminalis; Amy: Amygdala) are reciprocally connected and control information outflow.