Figure 5. Ontogeny of homeostatic control systems in rodents.

Interoceptive information about long-term energy stores is transmitted via neural projections from agouti-related peptide (AgRP) neurons (green arrows) and direct signaling via circulating factors (light blue arrows). Projections from AgRP neurons to downstream targets are not detected at birth. AgRP neuronal responsiveness to circulating leptin and ghrelin is observed within a week after birth; these signals regulate neurite outgrowth during lactation. A transient projection to the ventral tegmental area (VTA) is formed by postnatal day 7 (P7), and projections to the lateral hypothalamic area (LHA) and paraventricular nucleus of the hypothalamus (PVH) are fully formed by the end of lactation, AgRP circuits do not regulate homeostatic feeding behavior until P28. Thin dotted lines indicate the presence of a physical connection, but weak or immature signal transmission. Bold dashed lines represent signal transmission that is robust, but immature. Solid lines represent mature connections. Gray lines represent projections for which developmental datapoints are missing. Arrowheads represent excitatory inputs, while lines represent inhibitory inputs. Light blue circles represent sites that directly sense circulating signals of energy status (i.e. leptin and ghrelin).

Abbreviations: ARH, arcuate nucleus of the hypothalamus; BNST, bed nucleus of the stria terminalis; CeA, central nucleus of the amygdala; LHA,; NTS, nucleus of the solitary tract; P, postnatal day; PAG, periaqueductal gray; PB, parabrachial nucleus.