Dual roles in feeding for AMPA/kainate receptors: receptor activation or inactivation within distinct hypothalamic regions elicits feeding behavior

Hettes, Stacey R.; Gonzaga, James; Heyming, Theodore; Perez, Sam D.; Wolfsohn, Stefany D.; Stanley, B. Glenn

doi:10.1016/j.brainres.2003.08.032

Cited by 20 publications

(10 citation statements)

References 71 publications

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“…A number of different neuroactive substances have been reported in the VMH, including GABA, glutamate, nitric oxide, enkephalin, and dynorphin (Bhat et al, 1995;Commons et al, 1999;Ziegler et al, 2002;Slamberova et al, 2004;Lin et al, 2006). Glutamate appears to be the primary excitatory neurotransmitter in the medial hypothalamus (van den Pol et al, 1990), and glutamate agonists and antagonists have substantial effects on food intake (Hettes et al, 2003;Lee and Stanley, 2005). However, until now, there has not been any reliable means of selectively studying live glutamate neurons within the hypothalamus.…”

Section: Introductionmentioning

confidence: 99%

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

Pol²

2008

J. Neurosci.

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Anorexigenic melanocortins decrease food intake by activating MC3/MC4 receptors (MC3/4R); the prevailing view is that the orexigenic neuropeptide agouti-related peptide (AgRP) exerts the opposite action by acting as an antagonist at MC3/MC4 receptors. A total of 370 hypothalamic ventromedial nucleus (VMH) glutamatergic neurons was studied using whole-cell recording in hypothalamic slices from a novel mouse expressing green fluorescent protein (GFP) under control of the vesicular glutamate transporter 2 (vGluT2) promoter. Massive numbers of GFP-expressing VMH dendrites extended out of the core of the nucleus into the surrounding cell-poor shell. VMH dendrites received frequent appositions from AgRP-immunoreactive axons in the shell of the nucleus, but not the core, suggesting that AgRP may influence target VMH neurons. ␣-MSH, melanotan II (MTII), and selective MC3R or MC4R agonists were all inhibitory, reducing the spontaneous firing rate and hyperpolarizing vGluT2 neurons. The MC3/4R antagonist SHU9119 was excitatory. Unexpectedly, AgRP did not attenuate MTII actions on these neurons; instead, these two compounds showed an additive inhibitory effect. In the absence of synaptic activity, no hyperpolarization or change in input resistance was evoked by either MTII or AgRP, suggesting indirect actions. Consistent with this view, MTII increased the frequency of spontaneous and miniature IPSCs. In contrast, the mechanism of AgRP inhibition was dependent on presynaptic inhibition of EPSCs mediated by G i /G o -proteins, and was attenuated by pertussis toxin and NF023, inconsistent with mediation by G s -proteins associated with MC receptors. Together, our data suggest that the mechanism of AgRP actions on these excitatory VMH cells appears to be independent of the actions of melanocortins on MC receptors.

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Section: Introductionmentioning

confidence: 99%

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

Pol²

2008

J. Neurosci.

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“…Ex-4 was dissolved in sterile 0.9% NaCl for peripheral intraperitoneal (ip) injections and in sterile aCSF for electrophysiological studies. Both CNQX and MK-801 have been used extensively to probe the effects of glutamatergic signaling on food intake (8,11,17,22,27). Doses for drugs were selected from the literature (1,3,17,21,32).…”

Section: Drugsmentioning

confidence: 99%

The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors

Mietlicki‐Baase¹,

Ortinski

Rupprecht³

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

144

124

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“…S9, B and C). Pharmacological inhibition of glutamatergic signaling in the PVN has previously been shown to elicit intense feeding ( 18 ).…”

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confidence: 99%

The nutrient sensor OGT in PVN neurons regulates feeding

Lagerlöf

Slocomb

Hong

et al. 2016

Science

131

118

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Maintaining energy homeostasis is crucial for the survival and health of organisms. The brain regulates feeding by responding to dietary factors and metabolic signals from peripheral organs. It is unclear how the brain interprets these signals. O-GlcNAc transferase (OGT) catalyzes the posttranslational modification of proteins by O-GlcNAc and is regulated by nutrient access. Here, we show that acute deletion of OGT from αCaMKII-positive neurons in adult mice caused obesity from overeating. The hyperphagia derived from the paraventricular nucleus (PVN) of the hypothalamus, where loss of OGT was associated with impaired satiety. These results identify O-GlcNAcylation in αCaMKII neurons of the PVN as an important molecular mechanism that regulates feeding behavior.

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Dual roles in feeding for AMPA/kainate receptors: receptor activation or inactivation within distinct hypothalamic regions elicits feeding behavior

Cited by 20 publications

References 71 publications

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors

The nutrient sensor OGT in PVN neurons regulates feeding

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