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Regulation of Food Intake01:30

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Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
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Related Experiment Video

Updated: May 27, 2025

Fat Preference: A Novel Model of Eating Behavior in Rats
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Nutritionally responsive PMv DAT neurons are dynamically regulated during pubertal transition.

Cristina Sáenz de Miera1, Nicole Bellefontaine1, Marina A Silveira2,3

  • 1Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109.

Biorxiv : the Preprint Server for Biology
|February 20, 2025
PubMed
Summary

Energy balance impacts pubertal development. Dopamine transporter (DAT) neurons in the ventral premammillary nucleus (PMv) are identified as a key leptin receptor (LepRb) subpopulation, influencing sexual maturation via AVPV kisspeptin neurons.

Keywords:
Kiss1dopamine transporterhypothalamusleptinnutritionpuberty

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Area of Science:

  • Neuroendocrinology
  • Reproductive Biology
  • Metabolic Regulation

Background:

  • Pubertal development is intrinsically linked to energy balance and metabolic status.
  • Leptin signaling in the hypothalamus, particularly via leptin receptor (LepRb) neurons, is crucial for orchestrating the interplay between metabolism and reproduction.
  • The ventral premammillary nucleus (PMv) serves as a critical relay for leptin's reproductive actions.

Purpose of the Study:

  • To identify and characterize a novel subpopulation of leptin receptor-expressing neurons in the mouse PMv.
  • To investigate the role of these neurons, specifically those expressing the dopamine transporter (DAT), in regulating sexual maturation.
  • To elucidate the neuroanatomical connections and functional significance of PMvDAT neurons in the context of leptin signaling.

Main Methods:

  • Utilized genetic mouse models (DATCRE;tdTomato, DATCRE;Kiss1hrGFP) for cell-specific labeling and analysis.
  • Performed electrophysiological recordings to assess the membrane potential of PMvDAT neurons.
  • Quantified gene expression (Slc6a3, Lepr) in the PMv under different nutritional and hormonal conditions.
  • Employed viral tracing techniques to map projections from PMvDAT neurons.

Main Results:

  • Identified a novel subpopulation of PMv neurons co-expressing dopamine transporter (DAT) and leptin receptor (LepRb).
  • PMvDAT neurons express Lepr mRNA and respond to leptin, with distinct electrophysiological properties in prepubertal versus adult females.
  • Slc6a3 mRNA expression in the PMv is developmentally regulated and influenced by nutritional status and leptin levels.
  • PMvDAT neurons project to the anteroventral periventricular and periventricular nucleus (AVPV/PeN), surrounding kisspeptin neurons, with projections maturing with age.
  • These projections also target tyrosine hydroxylase neurons in adults.

Conclusions:

  • The DAT-expressing PMvLepRb subpopulation represents a novel neuronal circuit involved in leptin's regulation of sexual maturation.
  • These neurons likely influence reproductive timing by modulating the activity of AVPV kisspeptin/tyrosine hydroxylase neurons.
  • Findings highlight a critical link between metabolic state, dopamine signaling, and the neuroendocrine control of puberty.