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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

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Summary
This summary is machine-generated.

Leptin regulates pubertal development via novel dopamine transporter (DAT) expressing neurons in the ventral premammillary nucleus (PMv). These PMvDAT neurons, which express leptin receptors, influence sexual maturation by projecting to kisspeptin neurons.

Keywords:
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Area of Science:

  • Neuroendocrinology
  • Reproductive Biology
  • Metabolic Regulation

Background:

  • Pubertal development is intricately linked to energy balance and metabolic status.
  • Leptin signaling in the hypothalamus, particularly via leptin receptor (LepRb) neurons in the ventral premammillary nucleus (PMv), is crucial for reproductive regulation.
  • The precise neural circuits mediating leptin's reproductive effects remain incompletely understood.

Purpose of the Study:

  • To identify novel subpopulations of leptin receptor-expressing neurons in the PMv.
  • To investigate the role of dopamine transporter (DAT)-expressing PMv neurons in pubertal development and leptin signaling.
  • To elucidate the projections and potential targets of PMvDAT neurons in the female brain.

Main Methods:

  • Utilized genetically engineered mouse models (DATCRE; tdTomato, DATCRE; Kiss1hrGFP, Lepob).
  • Performed electrophysiological recordings to assess neuronal activity and membrane potential.
  • Quantified gene expression (Slc6a3, Lepr) via mRNA analysis.
  • Employed viral tracing techniques (adeno-associated virus) to map neuronal projections.

Main Results:

  • Identified a novel subpopulation of PMv neurons co-expressing the dopamine transporter (DAT) and leptin receptor (LepRb).
  • PMvDAT neurons are responsive to leptin and exhibit distinct electrophysiological properties in prepubertal versus adult females.
  • Slc6a3 mRNA expression in the PMv is influenced by nutritional status and leptin availability during development.
  • PMvDAT neurons project to the anteroventral periventricular and periventricular nucleus (AVPV/PeN), specifically targeting kisspeptin neurons, with projections maturing with age.
  • These projections are in close proximity to tyrosine hydroxylase neurons in adults.

Conclusions:

  • The DAT-expressing subpopulation of PMvLepRb neurons represents a key player in leptin's regulation of sexual maturation.
  • These neurons likely mediate leptin's effects on reproduction by influencing kisspeptin and tyrosine hydroxylase neurons within the AVPV/PeN.
  • This study reveals a novel neurocircuit involved in the metabolic control of reproduction.