The time of day that we eat has significant impact on body weight and metabolic health but what determines those mealtimes? In a new study
@NatureNeuro
, we monitored daily oscillations in the activity of key hypothalamic hunger neurons expressing AgRP. ++
Our trash panda made it to cover for the new issue of
@NatureNeuro
, highlighting our recent paper on the circuits encoding circadian feeding time.
Artwork by
@mikbalp
The time of day that we eat has significant impact on body weight and metabolic health but what determines those mealtimes? In a new study
@NatureNeuro
, we monitored daily oscillations in the activity of key hypothalamic hunger neurons expressing AgRP. ++
Brainstem is mainly associated with satiety while hunger signals are thought to act through hypothalamus. We describe NTS->PVN pathway activated by hunger signals & promotes feeding in part by adrenergic potentiation of GABA release onto PVN:MC4R neurons.+
Pleased to share our work on serotonergic regulation of appetite
@MolMetab
. We identified LH and BNST as relevant targets where optogenetic activation of dorsal raphe nucleus (DRN) sert+ projections suppresses feeding. 🧵
Opioids are generally known to promote hedonic appetite. Since most of the existing studies focused on mesolimbic reward circuits, the role of hypothalamic opioid signaling in appetite regulation remains unclear. In a new study from the lab we found that++
Direct ghrelin action on NOS1-expressing PVH neurons causes nitric oxide-mediated stimulation of HPA axis. We are happy to make a small contribution to this study led by
@NeurophysioLab
.
Excited to share the latest work from the lab
@npp_journal
. We examined activity dynamics of NTS catecholamine->PVN input in response to various stressors and showed that resulting inhibition of downstream PVN-MC4R neurons conveys negative valence.
We are pleased to be a part of this exciting study, led by Justin Grobe, describing a molecular mechanism for obesity-associated dysregulation in resting metabolic rate (RMR),through a switch in Ang-II receptor pathway in AgRP neurons.Congrats to all team.
Pleased to share our Preview with twitterless Connor Laule on the exciting work by Grzelka et al. describing hunger amplified synaptic drive onto AgRP neurons. Congratulations to
@FenselauHenning
and the team.
If you are interested in catecholamine and opioid dependent appetite-satiety & stress regulation, we will have 3 posters at SfN 2023 starting from tomorrow afternoon.
"...Activating Trh(Arc) neurons inhibits AgRP neurons and decreases feeding in an AgRP neuron-dependent manner. Silencing Trh(Arc) neurons increases feeding and body weight and reduces liraglutide’s satiating effects..."
3/ Our data suggest that, unlike their appetite promoting actions in reward pathways, opioids may contribute to satiety after eating via tonic AgRP-neuron inhibition. This work was jointly led by
@nillysayar
and
@yavuzyavuz1712
, in collaboration with
@LinTianPhD
lab and others.
“Caution must especially be exercised when the observed phenotype closely matches that of lesions in the area of use.Ensuring that expression in wild-type mice results in no observable changes or that neuronal cell densities are unaltered are two such methods of validating (AAV)”
Surprisingly, long term variations in AgRP neuron activity were not fully consistent with their assumed role as an energy homeostat -activated by hunger and silenced by feeding-. Instead, chronic AgRP neuron activity oscillated in parallel with past circadian feeding experience++
Wednesday morning Atasoy Lab poster at
#SfN2022
648.05/PP13 "Convergent modulation of feeding and stress by an ascending catecholamine pathway" Describing the gating of presynaptic release onto PVN-MC4R neurons by dorsal medullary adrenergic input. Presented by Connor Laule.
I'm extremely happy to announce that our project studying Store Operated Calcium Entry at presynaptic terminals is finally published!!
We asked whether SOCE can regulate neurotransmitter release and how.
See thread for details and cool findings!! 1/n
@yaksi_emre
We saw many examples of this under EM in mouse paraventricular hypothalamus, with clear evidence of recent dense core vesicle exocytosis at extrasynaptic varicosities ().
..such that AgRP activity was higher at the times of day when feeding occurred in recent past and lower at other times. For free feeding mice this was dark cycle and required intact SCN or light cue whereas for time restricted feeding this rise required DMH prodynorphin neurons++
2/ hypothalamic opioid levels surge after feeding, which, in turn, inhibit AgRP neurons through Mu-Opioid-Rs. MOR agonist DAMGO suppressed AgRP synaptic output and excitatory input onto them. We also uncovered conditional sensitivity to b-arrestin pathway inhibitors++
Rhythmic AgRP activation based on past experience could be an adaptation to ensure foraging in times of day during which successful feeding occurred in the past and to avoid it when it is futile or dangerous in an environment with rhythmic food availability.
These findings suggest that rather than classical homeostatic feedback regulation, AgRP-dependent hunger is more consistent with allostatic regulation in which AgRP activity changes in anticipatory fashion based on learned cues, in this case circadian time itself acting as a cue.
Congratulations to
@ronggong1
and
@BrainCaRMA
Lab team, elegantly showing a hindbrain double negative feedback loop required for sustained consumption.
See our new study in
@CellCellPress
, led by
@ronggong1
. She showed that neurons in the peri-locus coeruleus (periLC) are important for palatability-driven consumption of both food and water.
We also found 5HT levels and DRNsert axonal activity in LH and BNST increase with food and metabolic hormones. Finally, we showed that 5HT not only directly acts on LH neurons but can also presynaptically suppresses GABA release from AgRP axons, causing disinhibition.
@MunirGunesKutlu
Lasers from Doric. 4 independent channels of 450nm (~80mW each) was around $5k a few years ago, comes in as turn-key, no need for alignment.
Our new study in
@ScienceMagazine
, led by
@shengjin_xu
. We report CaRMA imaging-- a method that combines deep-brain in vivo single neuron dynamics in mice with detailed gene co-expression information in the same cells across multiple behavioral states.
@AshleyIngiosi
@CurrentBiology
@Inscopix
Congratulations, really beautiful video. Is that a capillary running through middle? Its baseline fluorescence levels seem to be responding as well..
These results confirm earlier cFos studies and provide insight into the role of non-HPA axis targets of ascending catecholamine fibers in stress response. This work was led by Connor Laule, a talented graduate student. Free full text can be accessed at:
Does anyone know a commercial source for AAV-CREoff-ChR2 (or a similar activating opsin) virus? All the available CREoff virus seems to be in combination with FLPon/off.
@Yippocampus
Great question, unfortunately our protocol does not permit doing this since food deprivation for such a long period would be too extreme for mice. Perhaps a more hunger resilient animal model would be more appropriate to address this.