Neuropeptide Y Cells Represent a Distinct Glucose-Sensing Population in the Lateral Hypothalamus

Sep 15, 2011Endocrinology

Neuropeptide Y cells are a unique group that senses glucose in the brain's lateral hypothalamus

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Abstract

Approximately 70% of lateral hypothalamic area NPY neurons are suppressed by increased extracellular glucose.

NPY, orexin, and melanin-concentrating hormone are expressed in distinct populations within the lateral hypothalamic area.
Subpopulations of NPY neurons in the lateral hypothalamic area were activated during both a 6-hour fast and insulin-induced low blood sugar.
Increased extracellular glucose led to hyperpolarization and activation of background potassium currents in a significant portion of LHA NPY neurons.
The glucose sensitivity of LHA NPY neurons differs notably from that of neighboring orexin and melanin-concentrating hormone neurons.
LHA NPY neurons may play a novel role in the brain's ability to monitor and respond to glucose levels.

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The maintenance of appropriate glucose levels is necessary for survival. Within the brain, specialized neurons detect glucose fluctuations and alter their electrical activity. These glucose-sensing cells include hypothalamic arcuate nucleus neurons expressing neuropeptide Y (NPY) and lateral hypothalamic area (LHA) neurons expressing orexin/hypocretins (ORX) or melanin-concentrating hormone (MCH). Within the LHA, a population of NPY-expressing cells exists; however, their ability to monitor energy status is unknown. We investigated whether NPY neurons located in the LHA, a classic hunger center, detect and respond to fluctuations in glucose availability and compared these responses with those of known LHA glucose sensors expressing ORX or MCH. Using mice expressing green fluorescent protein under the control of NPY regulatory elements, we identified LHA NPY cells and explored their anatomical distribution, neurochemical and electrical properties, in vivo responses to fasting and insulin-induced hypoglycemia, and in situ electrical responses to extracellular glucose. We report that NPY, ORX, and MCH are expressed in nonoverlapping populations within the LHA. Subpopulations of LHA NPY neurons were activated in vivo by both a 6-h fast and insulin-induced hypoglycemia. Likewise, increased extracellular glucose suppressed the electrical activity of approximately 70% of LHA NPY neurons in situ, eliciting hyperpolarization and activating background K+ currents. Furthermore, we report that the glucose sensitivity of LHA NPY neurons is significantly different from neighboring ORX and MCH neurons. These data suggest that NPY-expressing cells in the LHA are a novel population of glucose-sensing neurons that represent a new player in the brain circuitry integrating information about glucose homeostasis.

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Neuropeptide Y Cells Represent a Distinct Glucose-Sensing Population in the Lateral Hypothalamus

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