2025
Dorsal raphe nucleus MC4R-GABAergic neurons regulate feeding and anxiety
Yamagata S, Copperi F, White G, Kim J, Diano S. Dorsal raphe nucleus MC4R-GABAergic neurons regulate feeding and anxiety. Molecular Metabolism 2025, 99: 102199. PMID: 40602716, PMCID: PMC12275976, DOI: 10.1016/j.molmet.2025.102199.Peer-Reviewed Original ResearchConceptsDorsal raphe nucleusAnxiety-like behaviorDorsal raphe nucleus serotonin neuronsDorsal raphe nucleus neuronsWhole-body metabolismGlutamatergic populationsNeuronal populationsARC POMC neuronsCNS regulationSerotonin neuronsRaphe nucleusChemogenetic manipulationChemogenetic activationVGluT2 neuronsBrain areasMelanocortin receptor 4Paraventricular nucleusHypothalamic PVNSerotonin stainingPOMC neuronsArcuate nucleusSolitary tractMC4R neuronsNeuronal subpopulationsMetabolic regulationHypothalamic PNOC/NPY neurons constitute mediators of leptin-controlled energy homeostasis
Solheim M, Stroganov S, Chen W, Subagia P, Bauder C, Wnuk-Lipinski D, Del Río-Martín A, Sotelo-Hitschfeld T, Beddows C, Klemm P, Dodd G, Lundh S, Secher A, Wunderlich F, Steuernagel L, Brüning J. Hypothalamic PNOC/NPY neurons constitute mediators of leptin-controlled energy homeostasis. Cell 2025, 188: 3550-3566.e22. PMID: 40273910, DOI: 10.1016/j.cell.2025.04.001.Peer-Reviewed Original ResearchConceptsLeptin's anorectic effectsDiet-induced hyperphagiaNeuropeptide Y (NPYAgouti-related peptideChemogenetic activationAnorectic effectLeptin regulates appetiteBody weightArcuate nucleusLEPR expressionHyperphagiaLeptin actionSuppress appetiteObese backgroundLeptinObesity therapeuticsObesityNeuronsEnergy homeostasisWeight gainNPYNeurocircuitryAppetiteExpressionPNoCs
2024
Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity
Ahmed S, Polis B, Jamwal S, Sanganahalli B, MacDowell Kaswan Z, Islam R, Kim D, Bowers C, Giuliano L, Biederer T, Hyder F, Kaffman A. Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity. Brain Behavior And Immunity 2024, 122: 95-109. PMID: 39134183, PMCID: PMC11402597, DOI: 10.1016/j.bbi.2024.08.010.Peer-Reviewed Original ResearchEarly-life adversityModel of early-life adversityContextual fear conditioningLimited beddingFear conditioningSynaptic engulfmentLB miceSynaptic pruningSex-specific deficitsHippocampus of maleSex-specific effectsHippocampal deficitsAdolescent miceHippocampal functionEarly adversityChemogenetic activationSynaptic connectionsBehavioral aberrationsPotential compensatory mechanismsSynaptic abnormalitiesHippocampusAblation of microgliaRodent hippocampusDeficitsWeeks of lifeDevelopment of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release
Zhou X, Stine C, Prada P, Fusca D, Assoumou K, Dernic J, Bhat M, Achanta A, Johnson J, Pasqualini A, Jadhav S, Bauder C, Steuernagel L, Ravotto L, Benke D, Weber B, Suko A, Palmiter R, Stoeber M, Kloppenburg P, Brüning J, Bruchas M, Patriarchi T. Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release. Nature Communications 2024, 15: 5353. PMID: 38918403, PMCID: PMC11199706, DOI: 10.1038/s41467-024-49712-0.Peer-Reviewed Original ResearchConceptsOpioid peptide releaseVentral tegmental areaAcute brain slicesN/OFQ actionsChemogenetic activationIn vivo studiesNociceptin/orphanin FQTegmental areaFibre photometryOpioid peptidesBrain slicesPharmacological profileGenetically encoded sensorIntracellular signal transducersReceptor ligandsPeptide releaseMammalian brainFunctional relevanceNeuronsBehavioral processesSignal transducerReleasePotential interactionsRegulatory functionsN/OFQ
2023
146-OR: Causative Role of Hypothalamic Ventromedial Glucose-Inhibited Neurons in Impaired Counterregulatory Responses to Hypoglycemia
COPPERI F, SHEN X, DIANO S. 146-OR: Causative Role of Hypothalamic Ventromedial Glucose-Inhibited Neurons in Impaired Counterregulatory Responses to Hypoglycemia. Diabetes 2023, 72 DOI: 10.2337/db23-146-or.Peer-Reviewed Original ResearchImpaired counterregulatory responseCounterregulatory responsesGI neuronsRecurrent hypoglycemiaCausative roleGlucose-inhibited neuronsType 1 diabetesBlood glucose levelsScientific evidence pointsDiabetes CenterChemogenetic activationKidney diseaseVentromedial nucleusNeuronal activationGlucose levelsMouse modelCurrent evidenceConsecutive daysMiceNeuronsAdministrationSignificant decreaseCausal involvementNational InstituteHypoglycemia
2022
Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs
Mineur YS, Mose TN, Vanopdenbosch L, Etherington IM, Ogbejesi C, Islam A, Pineda CM, Crouse RB, Zhou W, Thompson DC, Bentham MP, Picciotto MR. Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs. Molecular Psychiatry 2022, 27: 1829-1838. PMID: 34997190, PMCID: PMC9106825, DOI: 10.1038/s41380-021-01404-7.Peer-Reviewed Original ResearchConceptsStress-related behaviorsCholinergic inputMedial septum/diagonal bandBehavioral effectsBrain ACh levelsChAT-positive neuronsSelective chemogenetic activationMuscarinic ACh receptorsDepression-like symptomsSignificant behavioral effectsHippocampal acetylcholineMaladaptive behavioral responsesAntidepressant effectsCholinergic neuronsACh releaseChemogenetic activationChemogenetic inhibitionCholinergic antagonistsLocal infusionAcetylcholine levelsACh levelsDiagonal bandACh receptorsHippocampal neuronsPharmacological approaches
2020
MC4R Signaling in Dorsal Raphe Nucleus Controls Feeding, Anxiety, and Depression
Bruschetta G, Jin S, Liu ZW, Kim JD, Diano S. MC4R Signaling in Dorsal Raphe Nucleus Controls Feeding, Anxiety, and Depression. Cell Reports 2020, 33: 108267. PMID: 33053350, DOI: 10.1016/j.celrep.2020.108267.Peer-Reviewed Original ResearchConceptsDorsal raphe nucleusNeuronal activationR neuronsDepressive-like behaviorMajor depressive disorderChemogenetic activationR miceChemogenetic inhibitionRaphe nucleusSerotonin levelsDepressive disorderMood behaviorΑ-MSHDRN infusionsControl feedingMiceWeight lossNeuronsSelective knockdownDepressionBehavioral phenotypesAnxietyActivationFeedingPRCPHypothalamic oestrogen receptor alpha establishes a sexually dimorphic regulatory node of energy expenditure
van Veen JE, Kammel LG, Bunda PC, Shum M, Reid MS, Massa MG, Arneson D, Park JW, Zhang Z, Joseph AM, Hrncir H, Liesa M, Arnold AP, Yang X, Correa SM. Hypothalamic oestrogen receptor alpha establishes a sexually dimorphic regulatory node of energy expenditure. Nature Metabolism 2020, 2: 351-363. PMID: 32377634, PMCID: PMC7202561, DOI: 10.1038/s42255-020-0189-6.Peer-Reviewed Original ResearchConceptsFemale-biased expressionMale-biased expressionSex-biased expressionSingle-cell RNA transcriptomicsPrecise neuronal populationsEstrogen receptor alphaReceptor alphaGene functionVentromedial hypothalamusRegulatory nodesRNA transcriptomicsMale developmentNeuronal populationsMouse ventromedial hypothalamusSitu hybridizationEnergy homeostasisEnergy expenditureCore temperatureExpressionTachykinin-1RPRMReduced core temperatureVMH neuronsChemogenetic activationPhysical activity
2019
Activation of Agrp neurons modulates memory-related cognitive processes in mice
Zimmer MR, Schmitz AE, Dietrich MO. Activation of Agrp neurons modulates memory-related cognitive processes in mice. Pharmacological Research 2019, 141: 303-309. PMID: 30610962, PMCID: PMC6400640, DOI: 10.1016/j.phrs.2018.12.024.Peer-Reviewed Original ResearchConceptsMemory-related cognitive processesCognitive processesMemory-related tasksBarnes maze taskBehavioral flexibilityAgRP neuronsSpontaneous alternation behaviorMaze taskSpatial learningY-maze testStereotyped behaviorAlternation behaviorFood intakeHypothalamic AgRP neuronsTaskNeuropeptide Y receptorsChemogenetic activationY receptorsMouse behaviorAdult miceMemoryNeuronsBehaviorLearningCritical regulator
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