TY - JOUR
T1 - Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone
AU - Liu, Tiemin
AU - Kong, Dong
AU - Shah, BhavikP
AU - Ye, Chianping
AU - Koda, Shuichi
AU - Saunders, Arpiar
AU - Ding, JunB
AU - Yang, Zongfang
AU - Sabatini, BernardoL
AU - Lowell, BradfordB
N1 - Funding Information:
We wish to thank M. Krashes, L. Vong, C. Bjorbaek, and J. Lu for helpful discussions; and B. Choi, X. Hu, S. Ma, and J. Yu for excellent technical support. This work was supported by grants from the National Institutes of Health (to B.B.L.: R01 DK089044, R01 DK071051, R37 DK053477, R01 DK075632, BNORC Transgenic Core-P30 DK046200 and BADERC Transgenic Core-P30 DK057521; to D.K.: a P&F from BADERC–P30 DK057521; to A.S.: F31 NS074842; to J.B.D.: K99 NS075136; to B.L.S.: NS046579) and the American Diabetes Association (to B.B.L.: Mentor-Based Postdoctoral Fellowship). A.S. is a recipient of a Shapiro predoctoral fellowship and J.B.D. is a recipient of a Parkinson's Disease Foundation postdoctoral fellowship (PDF-FBS-1106).
PY - 2012/2/9
Y1 - 2012/2/9
N2 - AgRP neuron activity drives feeding and weight gain whereas that of nearby POMC neurons does the opposite. However, the role of excitatory glutamatergic input in controlling these neurons is unknown. Toaddress this question, we generated mice lacking NMDA receptors (NMDARs) on either AgRP or POMC neurons. Deletion of NMDARs from AgRP neurons markedly reduced weight, body fat and food intake whereas deletion from POMC neurons had no effect. Activation of AgRP neurons by fasting, as assessed by c-Fos, Agrp and Npy mRNA expression, AMPA receptor-mediated EPSCs, depolarization and firing rates, required NMDARs. Furthermore, AgRP but not POMC neurons have dendritic spines and increased glutamatergic input onto AgRP neurons caused by fasting was paralleled by an increase in spines, suggesting fasting induced synaptogenesis and spinogenesis. Thus glutamatergic synaptic transmission and its modulation by NMDARs play key rolesin controlling AgRP neurons and determining the cellular and behavioral response to fasting.
AB - AgRP neuron activity drives feeding and weight gain whereas that of nearby POMC neurons does the opposite. However, the role of excitatory glutamatergic input in controlling these neurons is unknown. Toaddress this question, we generated mice lacking NMDA receptors (NMDARs) on either AgRP or POMC neurons. Deletion of NMDARs from AgRP neurons markedly reduced weight, body fat and food intake whereas deletion from POMC neurons had no effect. Activation of AgRP neurons by fasting, as assessed by c-Fos, Agrp and Npy mRNA expression, AMPA receptor-mediated EPSCs, depolarization and firing rates, required NMDARs. Furthermore, AgRP but not POMC neurons have dendritic spines and increased glutamatergic input onto AgRP neurons caused by fasting was paralleled by an increase in spines, suggesting fasting induced synaptogenesis and spinogenesis. Thus glutamatergic synaptic transmission and its modulation by NMDARs play key rolesin controlling AgRP neurons and determining the cellular and behavioral response to fasting.
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U2 - 10.1016/j.neuron.2011.11.027
DO - 10.1016/j.neuron.2011.11.027
M3 - Article
C2 - 22325203
AN - SCOPUS:84863012024
SN - 0896-6273
VL - 73
SP - 511
EP - 522
JO - Neuron
JF - Neuron
IS - 3
ER -