Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone
Authors: Chianping Ye
Shuichi Koda
Jun B Ding
Bernardo L Sabatini
Bhavik P Shah
Zongfang Yang
Tiemin Liu
Arpiar Saunders
Bradford B Lowell
Dong Kong
Journal: Neuron (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: AgRP neurons; POMC neurons; NMDA receptors; weight gain; food intake
Affiliations: Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA¬†02115,¬†USA.

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. To address 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 roles in controlling AgRP neurons and determining the cellular and behavioral response to fasting. 

Retracted: No

PubPeer comments:
 Upper L and R panels in Fig B seem to have overlapping elements.  , 
 We will look in to it. Thank you for pointing it out. , 
 Yes, thanks for point this out. Well look into it. , 
 Thank you for picking this out. We are checking this now and will update soon. , 
 Thanks for point this out. We are looking into it. , 
 #6 Thank you for your thorough response. , 
 We thank Pleopeltis Intermedia for pointing out this issue. We agree with Pleopeltis Intermedia that the two representative traces shown in Fig. 1B have overlapping elements. After communicating with the authors and searching our computers, we have identified the day when the tracings in question were first introduced into Figure 1 (Sept. 27, 2011) and the author who introduced the tracings. We have also uncovered an Excel spreadsheet that is linked to that Sept. 27 version of Figure 1, also generated by that same author. This spreadsheet contains the individual values for AMPAR-sEPSC frequency and amplitude obtained from brain slice recordings of 15 neurons from control mice and 15 neurons from knockout mice, as well as the statistical analysis of those values. The resulting means and SEMs were used to generate the bar graphs also shown in Fig. 1B, and the means and SEMs shown in that Excel spreadsheet are identical to those shown in Fig. 1B. These original traces upon which the quantitative values are based are stored on an old password-protected computer. Unfortunately, the author who used that computer, who retired in 2012, is unable to recall that password. Thus, at this point in time we are unable to learn more about the representative tracings that appear in Fig. 1B of the paper, or access the original traces upon which the quantitative values are based. That said, the findings summarized in the results section are unaffected by the representative tracings shown in Fig. 1B. Specifically, in the results section related to that figure we state, u201cdeletion of Grin1 in AgRP neurons did not significantly alter the frequency or, importantly, the amplitude of AMPAR-mediated spontaneous EPSCs (Figure 1B, right panel).u201d. This is the only thing that is concluded in our paper that has anything to do with the representative tracings in Fig. 1B. It is important to point out, however, that this conclusion was entirely based upon the quantitative analyses shown in the bar graphs in Fig. 1B and in the above-mentioned Excel spreadsheet, and not the representative tracings. We have no reason to doubt the validity of those quantitative analyses shown in Fig. 1B. In strong support of those results, the same finding is repeated in Fig. 6A (fed mouse groups) - a slight non-significant drop in AMPAR sEPSC frequency and no change in AMPAR sEPSC amplitude. Of note, the studies performed for the data in Fig. 6A were done at a different time, on different mouse slices and involved another electrophysiologist. Thus, at this point in time, we conclude that an unintentional mistake occurred in the image capture of the representative tracings shown in Fig. 1B, and that this mistake has no consequences for the findings related to that figure, or for the conclusions of our paper. Going forward, we will work with IT at our institution in an attempt to gain access to the old password protected computer on which we believe the complete set of tracings from 15 WT and 15 NR1 KO slices are stored. , 
 #6  Going forward, we will work with IT at our institution in an attempt to gain access to the old password protected computer on which we believe the complete set of tracings from 15 WT and 15 NR1 KO slices are stored. Any success in accessing the old password? , 
 We ve been unsuccessful in gaining access to the old computer. Based on information provided in my prior post, to the best of our ability, we view this issue as resolved. ,