Evidence map›Paper›PMID 28966976›Full record

ArticleeNeuro

Neurochemical Heterogeneity Among Lateral Hypothalamic Hypocretin/Orexin and Melanin-Concentrating Hormone Neurons Identified Through Single-Cell Gene Expression Analysis.

Laura E Mickelsen, Fredrick W Kolling, Brock R Chimileski, Akie Fujita, Carol Norris, Kun Chen, Craig E Nelson, Alexander C Jackson

Open access · goldAbstract read
In one paragraph

Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 119 citations in OpenAlex.

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  4. Dual Role of LH-GABA Neurons in Encoding Alcohol Reward and Aversive Memories.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
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  8. Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
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  10. Distinct lateral hypothalamic CaMKIIα neuronal populations regulate wakefulness and locomotor activity.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Emerging and upcoming therapies in insomnia.Translational and clinical pharmacology · 2024
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  15. Prostaglandin EProceedings of the National Academy of Sciences of the United States of America · 2023
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  16. Review
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  20. Review

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Laura E MickelsenDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.
Fredrick W KollingDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.
Brock R ChimileskiDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.
Akie FujitaDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.
Carol NorrisDepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269.
Kun ChenDepartment of Statistics, University of Connecticut, Storrs, CT 06269.
Craig E NelsonDepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269.
Alexander C JacksonDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.ORCID 0000-0001-7489-3946
University of Connecticut · US

Funding

Inhibitory Cell Types and Circuits in the Lateral HypothalamusR01MH112739 · NIMH · UNIVERSITY OF CONNECTICUT STORRS · PI Alexander Choi Jackson · 2017 to 2026
$5.1M
Synaptic Mechanisms of Hypothalamic Control of Vigilance and Cognitive FunctionR00MH097792 · NIMH · UNIVERSITY OF CONNECTICUT STORRS · PI JACKSON, ALEXANDER CHOI · 2013 to 2015
$734k
Leica TCS SP8 FSU AOBS 405 UV Spectral Confocal MicroscopeS10OD016435 · OD · UNIVERSITY OF CONNECTICUT STORRS · PI NISHIYAMA, AKIKO · 2014 to 2014
$456k
NIH HHS S10 OD016435NIMH NIH HHS R00 MH097792NIMH NIH HHS R01 MH112739
6 · The paper itself

Abstract

The lateral hypothalamic area (LHA) lies at the intersection of multiple neural and humoral systems and orchestrates fundamental aspects of behavior. Two neuronal cell types found in the LHA are defined by their expression of hypocretin/orexin (Hcrt/Ox) and melanin-concentrating hormone (MCH) and are both important regulators of arousal, feeding, and metabolism. Conflicting evidence suggests that these cell populations have a more complex signaling repertoire than previously appreciated, particularly in regard to their coexpression of other neuropeptides and the machinery for the synthesis and release of GABA and glutamate. Here, we undertook a single-cell expression profiling approach to decipher the neurochemical phenotype, and heterogeneity therein, of Hcrt/Ox and MCH neurons. In transgenic mouse lines, we used single-cell quantitative polymerase chain reaction (qPCR) to quantify the expression of 48 key genes, which include neuropeptides, fast neurotransmitter components, and other key markers, which revealed unexpected neurochemical diversity. We found that single MCH and Hcrt/Ox neurons express transcripts for multiple neuropeptides and markers of both excitatory and inhibitory fast neurotransmission. Virtually all MCH and approximately half of the Hcrt/Ox neurons sampled express both the machinery for glutamate release and GABA synthesis in the absence of a vesicular GABA release pathway. Furthermore, we found that this profile is characteristic of a subpopulation of LHA glutamatergic neurons but contrasts with a broad population of LHA GABAergic neurons. Identifying the neurochemical diversity of Hcrt/Ox and MCH neurons will further our understanding of how these populations modulate postsynaptic excitability through multiple signaling mechanisms and coordinate diverse behavioral outputs.

Indexed as

Action PotentialsAnimalsAnimals, NewbornFlow CytometryGene Expression RegulationGlucose Transporter Type 2Hypothalamic Area, LateralHypothalamic HormonesIn Vitro TechniquesLuminescent ProteinsMelaninsMiceMice, TransgenicMicrodissectionNeuronsNeuropeptidesGlucose Transporter Type 2Hypothalamic HormonesLuminescent Proteinsmelanin-concentrating hormoneMelaninsNeuropeptidesOrexinsPituitary HormonesRNA, MessengerSlc2a2 protein, mouseVesicular Inhibitory Amino Acid Transport ProteinsViaat protein, mousecotransmissionhypocretin/orexinlateral hypothalamic areamelanin-concentrating hormoneneuropeptideneurotransmitter

Identifiers

PMID28966976
PMCPMC5617207
OpenAlexW2751201726

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.