Distinct Roles for Specific Leptin Receptor Signals in the Development of Hypothalamic Feeding Circuits

• DOI: 10.1523/jneurosci.2277-11.2012
• Publication Date: 2012-01-26T03:32:26Z
• Authors: Sebastien G. Bouret; Sarah H. Bates; Stephen Chen; Martin G. Myers; Richard B. Simerly
• Keywords: Male; 0301 basic medicine; Hypothalamus; Mice, Transgenic; Feeding Behavior; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Organ Culture Techniques; Animals, Newborn; Neural Pathways; Animals; Humans; Receptors, Leptin; Nerve Net; Signal Transduction

Circulating hormones influence multiple aspects of hypothalamic development and play a role in directing formation of neural circuits. Leptin is secreted by adipocytes and functions as a key developmental signal that promotes axon outgrowth from the arcuate nucleus (ARH) during a discrete developmental critical period. To determine the cellular mechanisms by which leptin impacts development of hypothalamic circuits, we examined roles for leptin receptor (LepRb) signals in neonatal mice. LepRb, ERK, and STAT3 signaling were required for leptin-stimulated neurite outgrowth from ARH explantsin vitro. Neonatal mice with disrupted LepRb→ERK signaling displayed impaired ARH projections but were able to compensate by adulthood. LepRb→STAT3 signaling also plays a role in early circuit formation and controls the ultimate architecture of POMC, but not AgRP, projections. Thus, the developmental actions of leptin on feeding circuits are dependent on LepRb, and distinct signaling pathways are responsible for directing formation of NPY and POMC projections.