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. 2010 Sep 15;151(11):5395–5402. doi: 10.1210/en.2010-0681

Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice

Erika Gyengesi 1,a, Zhong-Wu Liu 1,a, Giuseppe D'Agostino 1, Geliang Gan 1, Tamas L Horvath 1, Xiao-Bing Gao 1, Sabrina Diano 1
PMCID: PMC2954711  PMID: 20843996

Abstract

Changes in circulating hormones, such as leptin and ghrelin, induce alterations in synaptic input organization and electrophysiological properties of neurons of the arcuate nucleus of the hypothalamus. To assess whether changes in circulating glucocorticoids also alter synaptic arrangement and membrane potential properties, we studied the effect of adrenalectomy (ADX) and corticosterone replacement in mice on the proopiomelanocortin (POMC) and neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus. ADX reduced the number of symmetric, putative inhibitory synapses onto POMC neurons and the number of asymmetric, putative excitatory synapses onto NPY/AgRP neurons. Corticosterone replacement in ADX mice to levels similar to sham-operated animals restored the number of synapses onto POMC and NPY/AgRP neurons to that seen in sham-operated controls. The alterations in the synaptic arrangement in ADX mice were not due to their decrease in food intake as evidenced by the synaptic analysis of the pair-fed control animals. In line with the altered synaptic input organization, a depolarization of POMC membrane potential and a hyperpolarization of NPY/AgRP membrane potential were observed in ADX mice compared with their sham-operated controls. All of these changes reverted upon corticosterone replacement. These results reveal that the known orexigenic action of corticosteroids is mediated, at least in part, by synaptic changes and altered excitability of the melanocortin system.

Glucocorticoids regulate synaptic plasticity and membrane potential properties of POMC and NPY/AgRP neurons of the arcuate nucleus of the hypothalamus.

The hypothalamus plays an important role in the regulation of many physiological phenomena, including energy expenditure, food intake, circadian rhythm, sleep, body temperature, blood pressure, and gonadal function (1,2,3,4).

Within the hypothalamus, neurons located in the arcuate nucleus (ARC) are highly responsive to many peripheral hormones, including leptin, insulin, glucocorticoids, ghrelin, thyroid hormones, and other signals as well (5,6). These peripheral hormones influence energy homeostasis either by activating or inhibiting the activity of the two antagonistic arcuate neuronal populations: the anorexigenic proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript-expressing neurons and the orexigenic agouti-related protein (AgRP) and neuropeptide Y (NPY)-containing neurons (for review, see ref. 5). During food deprivation, which is characterized by low levels of circulating leptin and thyroid hormone and high levels of corticosterone and ghrelin, NPY/AgRP neurons are activated and POMC/cocaine and amphetamine-regulated transcript neurons are inhibited. The intracellular events that occur in these neuronal populations have been the object of intense studies. Recent reports from our and other’s laboratories (7,8,9) have focused on the effect of hormones on synaptic mechanisms believed to play an important role in the regulation of the activity of these neurons.

Glucocorticoids play a key function in metabolism regulation. Many of the genetic models of obesity are characterized by elevated corticosterone levels. In addition, adrenalectomy (ADX) reduces food intake, fat stores, and body weight gain (for review, see Ref. 10). Corticosterone affects energy metabolism through central as well as peripheral mechanisms. Centrally, it has been shown that ADX induced an increase of POMC mRNA and Fos expression in α-MSH immunoreactive neurons in rats. In addition, ADX is able to reverse the obese phenotype and restore hypothalamic melanocortin tone in leptin-deficient ob/ob mice (11). Finally, ADX alters the sensitivity of the central melanocortin system to the effects of AgRP, the melanocortin antagonist (12). This effect is restored by corticosterone replacement (12).

Thus, the present study was carried out to assess the effect of changes in corticosterone levels on the synaptic properties of ARC NPY/AgRP and POMC neurons.

Materials and Methods

Animals

All procedures described below have been approved by the Institutional Animal Care and Use Committee of Yale University.

POMC/green fluorescent protein (GFP) and NPY/GFP-tagged mice were used in these studies (for details on the mice, please see Ref. 7). Briefly, two lines of bacterial artificial chromosome transgenic mice that express either τ-sapphire GFP under the transcriptional control of the NPY genomic sequence or τ-topaz GFP under the transcriptional control of POMC genomic sequence were generated (7). To confirm that GFP staining is only observed in areas where either POMC or NPY/AgRP neurons are expressed, we routinely analyze GFP staining. Briefly, free-floating 50-μm brain sections were incubated overnight with either AgRP (1:5000; Calbiochem, San Diego, CA) or anti-POMC (1:4000; Chemicon, Temecula, CA). Rhodamine antirabbit (AgRP) or antimouse (POMC) immunoglobulin (Jackson ImmunoResearch Laboratories, Inc., West Grove, PA) was used as secondary antibody. NPY-GFP mice were treated with colchicine to enhance cell body staining. Briefly, 45 h before perfusion, colchicine (40 μg in 2 μl saline) was injected into the lateral ventricle using a Hamilton syringe over a period of 10 min. Sections were examined for colocalization with GFP (without immunohistochemistry) using the appropriate filters and images collected using the multichannel module of the AxioVision Zeiss software (results not shown).

Animals were divided into three groups: sham-operated animals (control), ADX animals, and ADX animals with immediate corticosterone (ADX+C) replacement in their drinking water. Animals were housed individually and kept under standard laboratory conditions with free access to food and water. Bilateral ADX or a sham operation was performed under isoflurane anesthesia 8–10 d before starting the experiments.

Immediately after surgery, ADX mice received drinking water containing 0.9% (wt/vol) NaCl (Sigma, St. Louis, MO). An additional group of sham-operated animals was pair fed with the ADX group after the surgery.

For all animals, the body weight was measured before surgery and before killing. Their food intake was monitored daily before and after the surgery for the entire recovery time at the beginning of the light cycle. White adipose tissues (femoral, gonadal, retroperitoneal, and mesenteric fat pads) were collected to calculate the adiposity index. Animals were euthanized at the beginning of the light cycle (between 0900 and 1000 h) for all sets of the experiments.

Corticosterone treatments

Corticosterone treatment was initiated at the time of surgery by dissolving it (0.05 mg/ml; Sigma) (13) in ethanol and adding it to the drinking water to yield a final concentration of 2% ethanol. All of the other untreated groups were given similar drinking water without the hormone. To confirm that the daily water, and thereby, corticosterone intake reached the estimated amount and to ensure that the corticosterone supplementation did not alter fluid intake, we measured water consumption over 24 h.

Animals were killed during the light cycle (between 0900 and 1000 h). Plasma corticosterone was measured using an ELISA kit from Diagnostic Products Corp. (Los Angeles, CA).

Quantification of synaptic input onto GFP-POMC and GFP-NPY cells of the ARC

Adult male mice (age, 3 months) carrying GFP in either the POMC neurons (n = 20) or the NPY neurons (n = 20) were used in this study. Mice were divided into three groups: sham-operated controls (n = 5), ADX (n = 5), and ADX plus corticosterone replacement (n = 5). An additional group of sham-operated animals (n = 5) was pair fed. Ten days after surgery, animals were perfused at the beginning of the light cycle as previously described (9,13), and their brains were processed for GFP immunolabeling for electron microscopic examination. The unbiased stereological method for the assessment of synaptic number that was used is based upon our published paper (7,8,14). The central feature of this approach is the use of a systematic random sampling method, which meets the statistical requirements necessary to assure an unbiased estimate of the feature of interest.

The analysis of synapse number was performed in an impartial fashion as described elsewhere (7,14); a nonparametric ANOVA was selected for multiple statistical comparisons. The one-way ANOVA-test with Newman-Keuls post hoc test was used to determine significance of differences between groups. The statistical confidence was set at P < 0.05.

Electrophysiology

Whole-cell recordings were made from presumptive POMC and NPY neurons from the arcuate hypothalamic nucleus. Mice (age, 6 wk) were rapidly decapitated at the beginning of the light cycle and brains quickly dissected and 300 μm hypothalamic slices cut using a vibratome. Hypothalamic slices were maintained at 34 C and perfused with artificial cerebrospinal fluid. The bath solution (artificial cerebrospinal fluid) consisted of 124 mm NaCl, 3 mm KCl;, 2 mm CaCl2, 2 mm MgCl2, 1.23 mm NaH2PO4, 26 mm NaHCO3, and 2.5 mm glucose (pH 7.4) with NaOH and was continuously bubbled with 5% CO2 and 95% O2.

The patch pipettes were made of borosilicate glass (World Precision Instruments, Sarasota, FL) with a Sutter micropipette puller (P-97). The tip resistance of the recording pipettes was 2–4 MΩ after filling with a pipette solution containing 145 mm KMeSO4 [KCl replace KMeSO4 for miniature inhibitory postsynaptic current (mIPSC)], 1 mm MgCl2, 10 mm HEPES, 1.1 mm EGTA, 2 mm Mg-ATP, and 0.5 mm Na2-GTP (pH 7.3) with KOH. All data were sampled at 10 kHz and filtered at 3 kHz with a multiclamp 700B amplifier (Axon Instruments, Inc., Sunnyvale, CA) and the Apple Macintosh computer using Axograph X (Axon Instruments, Inc.). After a giga-ohm seal and a whole-cell access were achieved, the series resistance was between 5 and 12 MΩ and partially compensated by the amplifier. Both input and series resistance were monitored throughout the experiments.

The membrane potential was recorded under current clamp. The miniature excitatory postsynaptic currents (mEPSCs) was recorded under voltage clamp at −60 mV in the presence of tetrodotoxin (0.5 μm; Alomone Labs Ltd., Jerusalem, Israel) and picrotoxin (50 μm; Sigma-Aldrich, St. Louis, MO), or for mIPSCs in the presence of tetrodotoxin and 6-cyano-7-nitroquinoxaline-2,3-dione (10 μm; Sigma- Aldrich) plus 2-amino-5-phosphonovaleric acid-5 (50 μm; Sigma-Aldrich). GFP-POMC neurons were held at −60 mV. Frequency of mEPSCs (or mIPSCs) was generated after detection of mEPSCs (or mIPSCs) events.

Electrophysiological data were analyzed with Axograph X (Axon Instruments, Inc.) and plotted with Igor Pro software (WaveMetrics, Lake Oswego, OR).

Statistical analysis

Means were compared between experimental groups using one-way ANOVA with mean comparisons by the Student-Newman-Keuls method. A level of confidence of P < 0.05 was used to determine significant differences. Results are presented as mean ± se.

Results

Hormone measurements and body weight changes

Corticosterone levels were measured in all experimental groups. Its concentration in the sham-operated control group was 45.2 ± 7.1 ng/ml (Fig. 1A) and ADX significantly (P < 0.001) reduced it (10.6 ± 3.1 ng/ml) (Fig. 1A). Immediate corticosterone replacement after surgery showed a level that was not significantly different from that of control animals (57.5 ± 7.8 ng/ml). In the pair-fed group, corticosterone levels were also not significantly different from the controls (60.7 ± 13.0 ng/ml), although they were slightly elevated (Fig. 1A).

Figure 1.

Figure 1

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Corticosterone levels, food intake, body weight changes, and adiposity index of the different groups of animals. A, The level of corticosterone significantly decreased after ADX (10.6 ± 3.0 vs. 45.2 ± 7.1 ng/ml of control) and was restored to physiological levels (57.5 ± 7.8 ng/ml) by corticosterone treatment. B, Food intake of ADX animals significantly decreased compared with that of control groups. Corticosterone (ADX+C) replacement restored food intake to the value of controls. Pair-fed mice received an average of 3.18 ± 0.09 g/d. C, The body weight changes in control, ADX, ADX+C, and pair-fed mice. D, Graph showing the adiposity index of control, ADX, ADX+C, and pair-fed mice. *, P < 0.05 in all graphs.

After surgery, ADX animals consistently consumed about 15% less food (3.25 ± 0.13 g) per day than their sham operated counterparts (3.72 ± 0.17 g) (Fig. 1B). Corticosterone replacement to a group of ADX mice showed a food intake not significantly different to that of control mice (4.19 ± 0.10 g). The pair-fed group was given the same amount of food on average as the ADX group (3.18 ± 0.09 g) (Fig. 1B). As expected, ADX significantly reduced the body weight of the animals by −2.21 ± 1.3% compared with their weight before the surgery (P < 0.02). In both the sham operated and ADX+C groups, body weight gain increased (+1.85 ± 2.2 and +2.2 ± 2.4%, respectively) after surgery (Fig. 1C). The pair-fed group lost weight an average of −1.46 ± 1.7% from their original body weight (P < 0.05) (Fig. 1C). Analysis of the white adipose tissue mass from the different experimental groups showed that the adiposity index of the ADX group was significantly lower (1.89 ± 0.11) compared with the control group (2.98 ± 0.19) (P < 0.02).

Corticosterone replacement restored the adiposity index to the levels of sham controls (2.78 ± 0.08) (Fig. 1D).

Synaptology of POMC and NPY neurons

To assess whether changes in glucocorticoid levels affect the synaptology of POMC and NPY neurons of the ARC of the hypothalamus, we analyzed the synaptic input organization of these two neuronal populations (n = 5 per group). The number of symmetric and putative inhibitory synapses onto POMC cell bodies was significantly decreased in ADX animals (0.030 ± 0.004/μm) compared with sham controls (0.059 ± 0.012/μm; P = 0.04) and was restored by corticosterone replacement (0.059 ± 0.010/μm) (Fig. 2E). Pair-fed mice showed a symmetric synaptic density of 0.083 ± 0.015/μm. On the other hand, the number of asymmetric and putative excitatory synapses did not show any significant changes (sham, 0.043 ± 0.007/μm; ADX, 0.051 ± 0.010/μm; ADX+C, 0.050 ± 0.010/μm; and pair fed, 0.039 ± 0.004/μm) (Fig. 2E).

Figure 2.

Figure 2

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Synaptic plasticity in POMC and NPY/AgRP neurons. A–D, Electron micrographs of synapses on either POMC (GFP; A and B) or NPY (GFP; C and D) perikarya in the ARC. Black arrowheads point to symmetrical membrane specializations, and white arrowheads point to asymmetrical membrane specializations. Scale bar in D, 1 μm for A–D. E and F, Bar graphs showing the results of quantification of symmetrical and asymmetrical synapse number in the various experimental and control groups. *, P < 0.05. G1–G6, Electron micrographs of serial sections of a bouton that establishes asymmetrical synaptic membrane specialization (white arrowheads on G3–G6) with a POMC (GFP immunolabeled) perikaryon. H1–H5, Electron micrographs of serial sections of a bouton that establishes symmetrical membrane specialization (black arrowheads on H2–H4) with a POMC (GFP immunolabeled) perikaryon. Bar scale in H1, 1 μm for G and H.

In contrast to the POMC neurons, the number of asymmetric and putative excitatory synapses onto NPY neurons showed a significant decrease in ADX mice (0.018 ± 0.006/μm) compared with control (0.050 ± 0.012/μm; P = 0.04), ADX+C (0.042 ± 0.009/μm; P = 0.04), and pair-fed mice (0.067 ± 0.012/μm; P = 0.01) (Fig. 2F). No significant changes were observed in symmetric synapses (sham, 0.057 ± 0.011/μm; ADX, 0.041 ± 0.006/μm; ADX+C, 0.043 ± 0.008/μm; and pair fed, 0.038 ± 0.011/μm) (Fig. 2F).

Electrophysiological properties of POMC and NPY neurons

To assess whether the observed changes in synaptic input organization onto POMC and NPY neurons were associated with changes in membrane properties, we performed electrophysiological recordings from POMC and NPY neurons. The resting membrane potential of the POMC neurons of ADX mice (−57.13 ± 2.39 mV; n = 4 mice; total 18 cells) (Fig. 3A) was significantly more depolarized compared with sham controls (−63.39 ± 0.68 mV; n = 4 mice; total 21 cells; P < 0.05) (Fig. 3A). The resting membrane potential was restored to control levels (−65.47 ± 1.75 mV; n = 4 mice; total 18 cells) (P < 0.05) (Fig. 3A) by corticosterone replacement.

Figure 3.

Figure 3

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POMC and NPY/AgRP membrane potentials. Graphs showing the results of membrane potential measurements in POMC-GFP (A) and NPY/AgRP-GFP neurons (B) of control, ADX, and ADX+C-treated mice. ADX induced a depolarization and a hyperpolarization in the POMC and NPY/AgRP neurons, respectively. In both neuronal populations, corticosterone replacement restored membrane potential to the levels of control animals. *, P < 0.05.

On the other hand, the resting membrane potential of the NPY neurons of ADX mice was significantly more hyperpolarized (−57.41 ± 0.08 mV; n = 3 mice; total 9 cells) (Fig. 3B) compared with controls (−47.77 ± 1.76 mV; n = 3 mice; total 9 cells; P < 0.05) (Fig. 3B) and ADX+C mice (−47.89 ± 6.45 mV; n = 3 mice; total 8 cells; P < 0.05) (Fig. 3B).

To test whether these changes were due to alterations in potassium channel activity, we measured the potassium current in POMC neurons. No differences were found in ADX mice when compared with corticosterone-treated ADX controls (data not shown), suggesting that the depolarization of POMC neurons was indeed due to changes in synaptic arrangement.

In line with the changes in synaptic input organization, the frequency of mIPSCs in POMC neurons was significantly decreased in the ADX group (5.22 ± 0.48 Hz; n = 3 mice; total 21 cells) compared with controls (6.71 ± 0.21 Hz; n = 3 mice; total 16 cells; P < 0.05) (Fig. 4A). In addition, a significant increase in mEPSC in POMC neurons was also observed in ADX mice (8.00 ± 0.95 Hz; n = 3 mice; total 18 cells) compared with controls (4.56 ± 0.21 Hz; n = 3 mice; total 15 cells; P < 0.05) (Fig. 4B). In both cases, the values of mIPSC and mEPSC were restored to control levels by corticosterone replacement (7.56 ± 0.80 Hz and 3.26 ± 0.47, respectively; n = 3 mice per group; total 20 cells for mIPSC and 18 cells for mEPSC) (Fig. 4, A–D). No significant differences were observed in the amplitude of either mIPSCs or mEPSCs (Fig. 4, E and F, respectively).

Figure 4.

Figure 4

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Electrical properties of POMC-GFP neurons. A and B, In line with the results of the inhibitory input organization onto POMC neurons, the frequency of mIPSCs recorded from POMC-GFP neurons showed a significant decrease in ADX mice compared with controls (A). mEPSC of ADX animals also showed a significant increase in their frequency compared with that of controls (B). Both of these changes reverted upon corticosterone treatment. *, P < 0.05. C and D, Representative mIPSC (C) and mEPSC (D) traces from three POMC cells of the three experimental groups. E and F, Cumulative probability curves showing no differences between the ADX and control groups in the amplitudes of mIPSCs (E) and mEPSCs (F).

Discussion

Glucocorticoids regulate energy balance, food intake, and body weight through central and peripheral mechanisms. Our results provide evidence that corticosterone regulates anatomical as well as electrophysiological properties of POMC and NPY/AgRP neurons of the ARC that are important regulators of food intake and energy balance. Specifically, we have shown that corticosterone induces changes in the synaptic input organization onto POMC and NPY/AgRP neurons, which are associated with a depolarization of POMC and hyperpolarization of NPY/AgRP membrane potential after ADX. These changes in membrane potentials were due to presynaptic mechanisms as evidenced by the mIPSC and mEPSC recordings.

Our results are in agreement with the work of Rorato et al. (15), which showed that ADX induced an increase of POMC mRNA and Fos expression in α-MSH-immunoreactive neurons in rats.

This, together with our findings of a decreased inhibitory innervation onto POMC perykarya and the depolarization of POMC membrane potential, indicates that the resultant increased anorexigenic tone due to the activated POMC neurons in the hypothalamic ARC may be responsible, at least in part, for the reduced food intake and body weight gain that is exhibited after ADX. At the same time, we also observed a reduced excitatory input onto the NPY/AgRP neurons with a concomitant hyperpolarization of NPY/AgRP membrane potential, which may further contribute to the anorexigenic phenotype displayed in mice after ADX. These results are in agreement with a previous study by Akabayashi et al. (16), in which they showed that although ADX in rats has minimal impact on the hypothalamic NPY projection system and NPY gene expression and peptide content in the ARC, NPY content in the paraventricular nucleus, dorsomedial nucleus, and medial preoptic area, all NPY target regions, is markedly reduced after ADX.

In agreement with our findings of alterations in synaptic input organization and the resting membrane potentials of POMC and NPY/AgRP neurons, we found corresponding changes in the frequencies of mEPSC and mIPSC of POMC neurons in ADX mice. However, these changes were not followed by significant alterations in the amplitudes, indicating that critical changes do not occur at the postsynaptic sites. Moreover, although a change in mEPSCs was observed, the excitatory inputs onto the POMC neurons were not altered. This could be due to an increase in a pool of readily releasable glutamatergic vesicles. Future experiments will address this point.

The modification in the ratio of inhibitory to excitatory inputs onto the POMC and NPY/AgRP neurons raises the question of the origin of these projections. We have previously shown that the neighboring NPY/AgRP neurons send unidirectional projections to POMC neurons and that these synapses contain the inhibitory neurotransmitter γ-aminobutyric acid (17,18). Thus, considering the observed decrease in excitatory input onto the NPY/AgRP cells, it is conceivable that the overall reduction in the excitation of these neurons could then result in a decreased inhibitory input from these cells onto the POMC neurons. In addition to the neighboring NPY/AgRP cells, tyrosine hydroxylase-containing neurons of the hypothalamus have also been shown to project to the POMC neurons of the ARC, and these projections were found to be symmetric and thus putatively inhibitory in nature (17). Nevertheless, we cannot exclude the possibility that other parts of the brain that are responsive to changing glucocorticoid levels may be responsible for this altered inhibitory innervation of the POMC neurons.

The glutamatergic innervation of the NPY/AgRP neurons could originate from several areas of the brain, including local glutamatergic arcuate neurons (19) and/or other hypothalamic and extrahypothalamic systems. For example, the hypocretin system (or orexin) has been observed to greatly project to the ARC, where hypocretin receptors are highly expressed (20,21,22,23,24,25).

Lateral hypothalamic hypocretin mRNA has been shown to be significantly decreased in ADX animals and restored by glucocorticoid replacement (26,27). In addition, ARC activity must be intact in order for intracerebroventricular hypocretin administration to induce an orexinergic effect (28). Also, intracerebroventricular injection of hypocretin in ADX animals restores their food intake to the levels of sham-operated controls (12), thus supporting the hypothesis that the alterations in the circuit involving hypocretin, NPY/AgRP, and POMC neurons may be responsible for the differential food intake and body weight gain that occur after ADX.

In addition to the above, the role of glucocorticoids in the control of other systems regulated by the ARC of the hypothalamus should be considered. For example, arcuate POMC and NPY neurons are well known to regulate the activity of GnRH-producing neurons in the medial preoptic area (for review, see Ref. 29). Thus, changes in circulating levels of glucocorticoids, by affecting arcuate neuronal activities, may also affect reproduction. Indeed, this could be the cause of the disruption in the normal function of the hypothalamus seen in the hypothalamic amenorrhea (30).

Finally, our findings showing that changes in corticosterone levels induce changes in synaptic plasticity and electrical activity of hypothalamic neurons involved in the autonomic control of energy homeostasis are in agreement with many studies showing that changes in corticosterone levels also induce changes in hippocampal synaptic plasticity and LTP (for review, see Ref. 31). Thus, it is reasonable to suggest that the effect of corticosterone on synaptic plasticity and electrical activity of neurons is not an exclusive but a more generalized phenomenon affecting different areas of the brain.

In conclusion, our study shows that corticosterone, known to affect appetite and adiposity, alters the input organization of hypothalamic circuits, thus supporting the idea that synaptic plasticity of ARC feeding circuits are an inherent element in body weight regulation.

Acknowledgments

We thank Erzsebet Borok for her assistance with the EM processing.

Footnotes

Present address for E.G.: Prince of Wales Medical Research Institute and The University of New South Wales, Corner of Barker Street and Hospital Road, Randwick NSW 2031, Australia.

This work was supported by National Institutes of Health Grants DK 070039 (to S.D.) and DK 060711 (to T.L.H.) and American Diabetes Association 1-08-RA-36 (to S.D.).

Disclosure Summary: The authors have nothing to disclose.

First Published Online September 15, 2010

Abbreviations: ADX, Adrenalectomy; ADX+C, ADX animals with immediate corticosterone; AgRP, agouti-related protein; ARC, arcuate nucleus; GFP, green fluorescent protein; mIPSC, miniature inhibitory postsynaptic current; mEPSC, miniature excitatory postsynaptic current; NPY, neuropeptide Y; POMC, proopiomelanocortin.

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