Leptin responsive neurons project to the rostral preoptic area in mice — ASN Events
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  2. Poster Session 2 - Neuroendocrinology of Reproduction II
  3. Leptin responsive neurons project to the rostral preoptic area in mice

Leptin responsive neurons project to the rostral preoptic area in mice (#368)

Wieteke A Zuure 1 2 , Janette H Quennell 1 2 , Greg M Anderson 1 2
  1. Centre for Neuroendocrinology, University of Otago, Dunedin, Otago, New Zealand
  2. Department of Anatomy, University of Otago, Dunedin, Otago, New Zealand

Reproductive capacity is driven by gonadotropin releasing hormone (GnRH) released from GnRH neuron terminals into the portal bloodstream. The adipose tissue derived hormone leptin plays a critical role in the control of reproduction via signaling in the brain. The GnRH neurons do not have the receptors for leptin (Lepr) [1], therefore intermediate leptin responsive neurons that provide leptin-to-GnRH signaling must exist. Here the source of the leptin responsive neurons that provide input to the rostral preoptic area (rPOA), where GnRH cell bodies reside, are investigated. Fluorescent retrograde tracer beads (RetroBeads, Lumafluor) were injected into the rPOA of transgenic Lepr reporter mice (Lepr-eGFP). Uptake of the tracer by Lepr-eGFP neurons was assessed throughout the hypothalamus, with emphasis on regions that are leptin responsive and GABAergic (as these neurons play a critical role in leptin’s regulation of fertility [2]). Tracer uptake was most evident in the medial arcuate nucleus (Arc), the dorsomedial nucleus of the hypothalamus (DMN) and the ventral premammilary nucleus (PMV). Levels of tracer labeled cells that are also positive for Lepr-eGFP neurons were the highest in the medial Arc (18.7 ± 5.6%), lower in PMV (3.5 ± 2.7%), and close to absent in the DMN (1.1 ± 1.1%). To address whether GABAergic Lepr neurons in the Arc and DMN project to the rPOA, the above experiment was repeated in GABA reporter mice (Vgat-tdTomato). Interestingly, 24.1 ± 7.6% of tracer labeled neurons across the Arc were GABAergic, and uptake of tracer by GABAergic neurons in the DMN was again very low. These results suggest that both leptin responsive and GABAergic neurons from the Arc project to the region of the GnRH cell bodies. This work helps to narrow down the location and possible identity of critical mediators of leptin-to-GnRH signaling.

  1. Quennell, J.H., et al., Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology, 2009. 150(6): p. 2805-12.
  2. Zuure, W.A., et al., Leptin Signaling in GABA Neurons, But Not Glutamate Neurons, Is Required for Reproductive Function. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. 33(45): p. 17874-83.