Functional organization of neuronal and humoral signals regulating feeding behavior

Abstract

Energy homeostasis--ensuring that energy availability matches energy requirements--is essential for survival. One way that energy balance is achieved is through coordinated action of neural and neuroendocrine feeding circuits, which promote energy intake when energy supply is limited. Feeding behavior engages multiple somatic and visceral tissues distributed throughout the body--contraction of skeletal and smooth muscles in the head and along the upper digestive tract required to consume and digest food, as well as stimulation of endocrine and exocrine secretions from a wide range of organs. Accordingly, neurons that contribute to feeding behaviors are localized to central, peripheral, and enteric nervous systems. To promote energy balance, feeding circuits must be able to identify and respond to energy requirements, as well as the amount of energy available from internal and external sources, and then direct appropriate coordinated responses throughout the body.

Figure 1

Outline of circuits involved in controlling feeding behavior. The diagram depicts a subset of the neuronal connections reported to influence feeding, chosen to highlight opportunities for integration between different classes of inputs (red arrows) and outputs (blue arrows). These inputs and outputs are transmitted via neuronal projections (solid lines) as well as humoral factors (dotted lines). Note that arrows reflect connectivity between two brain regions and not an actual anatomical pathway. Interoceptive inputs transmit information about energy availability that is essential for homeostatic regulation of food intake. Sensory meal-related signals from the alimentary tract are relayed to the brain through autonomic and sensory nerves, as well as humoral factors. Cognitive inputs are required for volitional feeding; food-related cues are processed in cortico-limbic circuits to confer learned aspects of feeding as well as to determine the reward value of food. A state of arousal is transmitted by neurons in the LHA to a network of highly interconnected neurons in the hypothalamus and brainstem. Feeding behavior is directed through the coordinated signals of three classes of output pathways. Somatomotor outputs from brain stem CPGs direct the muscular contractions needed to seek and consume food. Visceromotor outputs through the autonomic nervous system regulate the secretion of factors involved in nutrient processing, metabolism and storage. Neurosecretory outputs regulate the release of pituitary hormones that influence feeding behavior. Abbreviations: ARH, arcuate nucleus of the hypothalamus; BST, bed nuclei of the stria terminalis; CPG, central pattern generator; DMH, dorsomedial nucleus of the hypothalamus; DVC dorsovagal complex (area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus); LHA, lateral hypothalamic area; LS, lateral septum; NAc, nucleus accumbens; PVH, paraventricular nucleus of the hypothalamus; SN, substantia nigra; VTA, ventral tegmental area.

Figure 2

Outline of pathways mediating contextual cues to feeding circuits. Several classes of contextual signals ensure that the circuit response to a given stimulus is appropriate for the internal and external conditions. Contextual inputs (outlined in color) facilitate adaptations in circuit activity to coordinately modulate the strength of interoceptive, cognitive and arousal inputs (arrows from Figure 1 outlined in gray). These modulatory influences are conveyed by neuronal projections (solid lines) as well as humoral factors (dotted lines). Nutrient and peptide hormone signals of short- and long-term energy status (green arrows) are relayed from the viscera. Circadian inputs (blue arrows) are relayed from light-activated circuits in the SCN, which transmits humoral and neuronal signals to hypothalamic nuclei implicated in feeding regulation and arousal. Visceral stress signals (red arrows) are integrated with interoceptive inputs in the brainstem that regulate feeding and are also transmitted to midbrain nuclei regulating gastrointestinal malaise (PB). Emotional stressors (red arrows) are integrated with other cognitive inputs in corticolimbic circuits to the PVH; stress factors produced in the brain and periphery feed back to cognitive circuits to encourage or suppress motivated feeding behavior. Abbreviations: ARH, arcuate nucleus of the hypothalamus; BST, bed nuclei of the stria terminalis; CPG, central pattern generator; DMH, dorsomedial nucleus of the hypothalamus; DVC dorsovagal complex (area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus); LHA, lateral hypothalamic area; LS, lateral septum; NAc, nucleus accumbens; PB, parabrachial nucleus; PVH, paraventricular nucleus of the hypothalamus; SCN, suprachiasmatic nucleus; SN, substantia nigra; VTA, ventral tegmental area.