Distribution and Activation of Melanin-Concentrating Hormone Receptor-1 at Dopaminergic, GABAergic, and Glutamatergic Neurons in the Ventral Tegmental Area
Bibliographic record
Abstract
Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide that acts through its receptor (MCHR1) to promote positive energy balance by increasing food intake and decreasing energy expenditure.MCH has been shown to inhibit dopamine release from the mesocorticolimbic dopamine pathway originating in the ventral tegmental area (VTA), and a hyperdopaminergic state underlies hyperactivity observed in animals lacking MCH or MCHR1.However, it is not known if the inhibitory effect of MCH on dopaminergic tone could be due to direct regulation of dopaminergic VTA neurons.We used a combination of molecular, neuroanatomical, and electrophysiological techniques to assess MCHR1 expression and activation in the VTA.MCH neurons project to the VTA, which comprises nerve terminals that contain MCH and may represent MCH release sites.Consistent with this, we detected MCHR1 expression on major VTA cell types, including those that are dopaminergic, GABAergic, and glutamatergic.Functional MCHR1 activation may regulate dopamine release via two mechanisms, one by acutely and directly inhibiting dopaminergic VTA neurons, and the other by disinhibiting glutamatergic afferents to dopaminergic VTA neurons.While we have not measured dopamine release in this present thesis, we postulate that MCH may acutely suppress dopamine release, while concurrently engaging local glutamatergic signaling to restore dopamine levels.These results signify that the VTA is a novel target for MCH-mediated physiology, including for the maintenance of energy homeostasis.their help and for making lab all the more enjoyable.Special thanks to Ralitsa Nikolova for her help analyzing ISH signal, Mikayla Payant for helping with anterograde injection studies, and Jesukhogie Williams-Ikhenoba for his help with gene and protein expression studies.Additional thanks to Bianca Bono for helping to prepare tissue and establish a combined ISH and IHC protocol.Thank you to the Mighty 93.1, CKCU FM, for always having fantastic programming to listen to and for allowing me to host my own show "Track 11" (https://cod.ckcufm.com/programs/518/info.html).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".