MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus
| Autor: | Shah, Bhavik P, Vong, Linh, Olson, David P, Koda, Shuichi, Krashes, Michael J, Ye, Chianping, Yang, Zongfang, Fuller, Patrick M, Elmquist, Joel K, Lowell, Bradford B |
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| Rok vydání: | 2014 |
| Předmět: |
Injections
Stereotaxic Techniques Mice Glutamates Basic Helix-Loop-Helix Transcription Factors Animals Obesity GABAergic Neurons Nutrition Neurons Integrases Body Weight Neuropeptides Neurosciences Reproducibility of Results Feeding Behavior Dependovirus Parabrachial Nucleus Repressor Proteins Synapses Melanocortin Vesicular Glutamate Transport Protein 2 Type 4 Energy Metabolism Gene Deletion Paraventricular Hypothalamic Nucleus Receptor |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 111, iss 36 |
| Popis: | Activation of melanocortin-4 receptors (MC4Rs) restrains feeding and prevents obesity; however, the identity, location, and axonal projections of the neurons bearing MC4Rs that control feeding remain unknown. Reexpression of MC4Rs on single-minded 1 (SIM1)(+) neurons in mice otherwise lacking MC4Rs is sufficient to abolish hyperphagia. Thus, MC4Rs on SIM1(+) neurons, possibly in the paraventricular hypothalamus (PVH) and/or amygdala, regulate food intake. It is unknown, however, whether they are also necessary, a distinction required for excluding redundant sites of action. Hence, the location and nature of obesity-preventing MC4R-expressing neurons are unknown. Here, by deleting and reexpressing MC4Rs from cre-expressing neurons, establishing both necessity and sufficiency, we demonstrate that the MC4R-expressing neurons regulating feeding are SIM1(+), located in the PVH, glutamatergic and not GABAergic, and do not express oxytocin, corticotropin-releasing hormone, vasopressin, or prodynorphin. Importantly, these excitatory MC4R-expressing PVH neurons are synaptically connected to neurons in the parabrachial nucleus, which relays visceral information to the forebrain. This suggests a basis for the feeding-regulating effects of MC4Rs. |
| Databáze: | OpenAIRE |
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