Developmental switch of leptin signaling in arcuate nucleus neurons

Arian F. Baquero, Alain J. de Solis, Sarah R. Lindsley, Melissa A. Kirigiti, M. Susan Smith, Michael A. Cowley, Lori M. Zeltser, Kevin L. Grove

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    35 Scopus citations

    Abstract

    Leptin is well known for its role in the regulation of energy homeostasis in adults, a mechanism that at least partially results from the inhibition of the activity of NPY/AgRP/GABA neurons (NAG) in the arcuate nucleus of the hypothalamus (ARH). During early postnatal development in the rodent, leptin promotes axonal outgrowth from ARH neurons, and preautonomic NAG neurons are particularly responsive to leptin's trophic effects. To begin to understand how leptin could simultaneously promote axonal outgrowth from and inhibit the activity of NAG neurons, we characterized the electrochemical effects of leptin on NAG neurons in mice during early development. Here, we show thatNAG neurons do indeed express a functional leptin receptor throughoutthe early postnatal period in the mouse; however, at postnatal days 13-15, leptin causes membrane depolarization in NAG neurons, rather than the expected hyperpolarization. Leptin action on NAG neurons transitions from stimulatory to inhibitory in the periweaning period, in parallel with the acquisition of functional ATP-sensitive potassium channels. These findings are consistentwith the idea thatleptin provides an orexigenic drive through the NAG system to help rapidly growing pups meet their energy requirements.

    Original languageEnglish (US)
    Pages (from-to)9982-9994
    Number of pages13
    JournalJournal of Neuroscience
    Volume34
    Issue number30
    DOIs
    StatePublished - Jan 1 2014

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    Keywords

    • Arcuate nucleus
    • Development
    • Leptin
    • Mouse
    • NPY

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Baquero, A. F., de Solis, A. J., Lindsley, S. R., Kirigiti, M. A., Susan Smith, M., Cowley, M. A., Zeltser, L. M., & Grove, K. L. (2014). Developmental switch of leptin signaling in arcuate nucleus neurons. Journal of Neuroscience, 34(30), 9982-9994. https://doi.org/10.1523/JNEUROSCI.0933-14.2014