5
Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop.
Cell. 2011 Sep 16; 146(6):992-1003
All selected articles haveThis article has been added to your saved articles
You can follow/unfollow articles via MyF1000 or via the article or browse pages.
10 Oct 2011
New Finding
DOI: 10.3410/f.13336052.14702188
I found this paper exciting because it presents convincing data for the existence of a positive feedback loop in agouti-related peptide (AGRP)/neuropeptide Y (NPY) hypothalamic neurons between the action of the orexigenic hormone ghrelin and the ryanodine receptor, which releases Ca2+ from intracellular...Continue reading
I found this paper exciting because it presents convincing data for the existence of a positive feedback loop in agouti-related peptide (AGRP)/neuropeptide Y (NPY) hypothalamic neurons between the action of the orexigenic hormone ghrelin and the ryanodine receptor, which releases Ca2+ from intracellular stores.
Ghrelin activates a Gq-coupled receptor, which results in release of Ca2+ from the endoplasmic reticulum. This Ca2+ activates CaMKK2, which in turn activates the 5' AMP-activated protein kinase (AMPK). AMPK then activates the ryanodine receptor to release Ca2+, thus completing the loop. The technology used in this study is elegant, and the discovery of this feedback signaling loop and how it generates a flip-flop memory circuit to sustain activity states by transient exposure to hormones are profound.
Ghrelin activates a Gq-coupled receptor, which results in release of Ca2+ from the endoplasmic reticulum. This Ca2+ activates CaMKK2, which in turn activates the 5' AMP-activated protein kinase (AMPK). AMPK then activates the ryanodine receptor to release Ca2+, thus completing the loop. The technology used in this study is elegant, and the discovery of this feedback signaling loop and how it generates a flip-flop memory circuit to sustain activity states by transient exposure to hormones are profound.
Disclosures
None declared
Add Comment
Means A: F1000Prime Recommendation of [Yang Y et al., Cell 2011, 146(6):992-1003]. In F1000Prime, 10 Oct 2011; DOI: 10.3410/f.13336052.14702188. F1000Prime.com/13336052#eval14702188
25 Oct 2011
New Finding
DOI: 10.3410/f.13336052.14726142
This intriguing work highlights a novel mechanism by which a behavioral state may be actively maintained downstream of hormone actions by changes in synaptic activity. An interesting aspect of this mechanism is that it permits modulation by facilitating and opposing inputs, which is adaptive for a lterm...Continue reading
This intriguing work highlights a novel mechanism by which a behavioral state may be actively maintained downstream of hormone actions by changes in synaptic activity. An interesting aspect of this mechanism is that it permits modulation by facilitating and opposing inputs, which is adaptive for a longer-term behavioral propensity such as hunger.
An interesting question is how these mechanisms adapt to the natural growth during the post-weaning period; is the synaptic excitation increased on the neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons, is it more prolonged, or conversely, is the inhibition on the pro-opiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons increased?
It is probably worth pointing out that methylxanthines such as caffeine are unlikely to affect this system in concentrations that are encountered in daily coffee use!
An interesting question is how these mechanisms adapt to the natural growth during the post-weaning period; is the synaptic excitation increased on the neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons, is it more prolonged, or conversely, is the inhibition on the pro-opiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons increased?
It is probably worth pointing out that methylxanthines such as caffeine are unlikely to affect this system in concentrations that are encountered in daily coffee use!
Disclosures
None declared
Colmers W: F1000Prime Recommendation of [Yang Y et al., Cell 2011, 146(6):992-1003]. In F1000Prime, 25 Oct 2011; DOI: 10.3410/f.13336052.14726142. F1000Prime.com/13336052#eval14726142
F1000Prime Recommendations, Dissents and Comments for [Yang Y et al., Cell 2011, 146(6):992-1003]. In F1000Prime, 19 Jun 2013; F1000Prime.com/13336052
Only registered/signed-in users can make comments.
Sign in or Subscribe to create your user account and join the discussion.
Sign in or Subscribe to create your user account and join the discussion.
No comments yet.
Synaptic plasticity in response to changes in physiologic state is coordinated by hormonal signals across multiple neuronal cell types. Here, we combine cell-type-specific electrophysiological, pharmacological, and optogenetic techniques to dissect neural circuits and molecular pathways controlling synaptic plasticity onto AGRP neurons, a population that regulates feeding. We find that food deprivation elevates excitatory synaptic input, which is mediated by a presynaptic positive feedback loop involving AMP-activated protein kinase. Potentiation of glutamate release was triggered by the orexigenic hormone ghrelin and exhibited hysteresis, persisting for hours after ghrelin removal. Persistent activity was reversed by the anorexigenic hormone leptin, and optogenetic photostimulation demonstrated involvement of opioid release from POMC neurons. Based on these experiments, we propose a memory storage device for physiological state constructed from bistable synapses that are flipped between two sustained activity states by transient exposure to hormones signaling energy levels.
Copyright © 2011 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.cell.2011.07.039
PMID: 21925320
