Development of "Hunger Neurons" and the Unanticipated Relationship Between Energy Metabolism and Mother-Infant Interactions

Abstract

Over the course of a lifetime, the perinatal period plays an outsized role in the function of physiological systems. Here, we discuss how neurons that regulate energy metabolism contribute to the infant's relationship with the mother. We focus our discussion on Agrp neurons, which are located in the arcuate nucleus of the hypothalamus. These neurons heavily regulate energy metabolism. Because offspring transition from a period of dependence on the caregiver to independence, we discuss the importance of the caregiver-offspring relationship for the function of Agrp neurons. We present evidence that in the adult, Agrp neurons motivate the animal to eat, while in the neonate, they motivate the offspring to seek the proximity of the caregiver. We specifically highlight the peculiarities in the development of Agrp neurons and how they relate to the regulation of metabolism and behavior over the course of a lifetime. In sum, this review considers the unique insights that ontogenetic studies can offer toward our understanding of complex biological systems, such as the regulation of energy metabolism and mother-infant attachment.

Keywords: Development; Diabetes; Energy balance; Hypothalamus; Melanocortin system; Metabolism; Mother-infant relationship; Obesity.

Figure 1.

Illustration of the rodent brain pointing to the location of the hypothalamus. In the coronal section, it is possible to observe the location of the hypothalamus. At the base of the hypothalamus is the arcuate nucleus where Agrp and POMC neurons reside. Agrp neurons reside in a more medial part of the arcuate nucleus, surrounding the medial eminence and the third ventricle. POMC neurons are intermingled with Agrp neurons and also reside more laterally in the arcuate nucleus.

Figure 2.. Models of Agrp neuron activity in neonates and adults.

(A) In neonates, deprivation of maternal cues, which generates a state of distress, activates Agrp neurons. The activation of Agrp neurons participates of a physiological response that increases crying and the proximity of the neonate to the mother (e.g., increasing maternal approach and care). Contact with the mother inhibits the activity of Agrp neurons. (B) Model with parallel degrees of analysis, but illustrating the modulation of Agrp neurons in adults. Caloric deprivation, which generates a state of hunger, activates Agrp neurons. Activation of Agrp neurons participates of a physiological response that increases food seeking behavior and ultimately food ingestion. Food ingestion inhibits the activity of Agrp neurons.

Figure 3.. Activity of Agrp neurons and their consequent proximal and ultimate causations.

In adults, the activity of Agrp neurons motivate the animal to eat to restore homeostasis. In this regard, food deprivation leads to activation of Agrp neurons and food consumption suppresses the activity of these neurons. Thus, the nutritional status of the animal and the availability of nutrients provide direct feedback to modulate the activity of Agrp neurons. In neonates, the direct feedback provided by the nutritional status of the animal and the current availability of nutrients do not seem to directly affect the activity of the Agrp neurons. It is the proximity of the mother, however, that modulates Agrp neuron activity. Separation of the mother increases, while reunion with the mother decreases the activity of Agrp neurons. An increase in the activity of Agrp neurons motivates the infant to seek proximity of the mother, which in turn will promote restoration of the homeostasis.