Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone

Tiemin Liu, Dong Kong, BhavikP Shah, Chianping Ye, Shuichi Koda, Arpiar Saunders, JunB Ding, Zongfang Yang, BernardoL Sabatini, BradfordB Lowell

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)511-522
Number of pages12
JournalNeuron
Volume73
Issue number3
DOIs
StatePublished - Feb 9 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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    Liu, T., Kong, D., Shah, B., Ye, C., Koda, S., Saunders, A., Ding, J., Yang, Z., Sabatini, B., & Lowell, B. (2012). Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron, 73(3), 511-522. https://doi.org/10.1016/j.neuron.2011.11.027