Details

Autor(en) / Beteiligte

• Krashes, Michael J.
• Shah, Bhavik P.
• Madara, Joseph C.
• Olson, David P.
• Strochlic, David E.
• Garfield, Alastair S.
• Vong, Linh
• Pei, Hongjuan
• Watabe-Uchida, Mitsuko
• Uchida, Naoshige
• Liberles, Stephen D.
• Lowell, Bradford B.

Titel

An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger

Ist Teil von

• Nature (London), 2014-03, Vol.507 (7491), p.238-242

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2014

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• The AgRP-expressing neurons in the arcuate nucleus drive food-seeking behaviours during caloric restriction; a mouse study of monosynaptic retrograde rabies spread and optogenetic circuit mapping reveals that these neurons are activated by input from hypothalamic paraventricular nucleus cells and their activation or inhibition can modulate feeding behaviour. The neurons that prescribe hunger Increasing activity of the AgRP neurons in the hypothalamus drives food-seeking behaviours during periods of calorie restriction. The source of the input that provokes this hunger response was unknown. Bradford Lowell and colleagues have now mapped the inputs into these AgRP neurons and demonstrate that the paraventricular nucleus, normally thought of as a satiety centre, contains orexigenic neurons that drive AgRP neurons and food-seeking in mice, even when the mouse was otherwise sated. This work establishes specific populations of paraventricular nucleus neurons as drivers of a powerful hub within the feeding circuit. Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake 1 , 2 , 3 , 4 , 5 . Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding 3 , 6 , 7 . Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity 8 , 9 , 10 . Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.