AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors.
It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit-impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing-dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors.
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Marcelo O
MO
Dietrich
Jeremy
J
Bober
Jozélia G
JG
Ferreira
Luis A
LA
Tellez
Yann S
YS
Mineur
Diogo O
DO
Souza
Xiao-Bing
XB
Gao
Marina R
MR
Picciotto
Ivan
I
Araújo
Zhong-Wu
ZW
Liu
Tamas L
TL
Horvath
D054369:Agouti-Related Protein / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine; D059290:Dopaminergic Neurons / Q000502:physiology*; D005260:Female; D055785:Gene Knockdown Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D012201:Reward
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D003042:Cocaine; D004298:Dopamine