Parabrachial opioidergic projections to preoptic hypothalamus mediate behavioral and physiological thermal defenses

Maintaining stable body temperature through environmental thermal stressors requires detection of temperature changes, relay of information, and coordination of physiological and behavioral responses. Studies have implicated areas in the preoptic area of the hypothalamus (POA) and the parabrachial nucleus (PBN) as nodes in the thermosensory neural circuitry and indicate that the opioid system within the POA is vital in regulating body temperature. In the present study we identify neurons projecting to the POA from PBN expressing the opioid peptides dynorphin and enkephalin. Using mouse models, we determine that warm-activated PBN neuronal populations overlap with both prodynorphin (Pdyn) and proenkephalin (Penk) expressing PBN populations. Here we report that in the PBN Prodynorphin (Pdyn) and Proenkephalin (Penk) mRNA expressing neurons are partially overlapping subsets of a glutamatergic population expressing Solute carrier family 17 (Slc17a6) (VGLUT2). Using optogenetic approaches we selectively activate projections in the POA from PBN Pdyn, Penk, and VGLUT2 expressing neurons. Our findings demonstrate that Pdyn, Penk, and VGLUT2 expressing PBN neurons are critical for physiological and behavioral heat defense.

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Parabrachial Opioidergic Projections to Preoptic Hypothalamus Mediate Behavioral and Physiological Thermal Defenses

10.1101/2020.06.23.167619 ◽

2020 ◽

Author(s):

Aaron J. Norris ◽

Jordan R. Shaker ◽

Aaron L. Cone ◽

Imeh B. Ndiokho ◽

Michael R Bruchas

Keyword(s):

Body Temperature ◽

Opioid Peptides ◽

Behavioral Responses ◽

Neural Circuitry ◽

Opioid System ◽

Parabrachial Nucleus ◽

Hypothalamic Area ◽

Temperature Changes ◽

Neuronal Populations

SummaryMaintaining stable body temperature through environmental thermal stressors requires detection of temperature changes, relay of information, and coordination of physiological and behavioral responses. Studies have implicated areas in the preoptic hypothalamic area (POA) and the parabrachial nucleus (PBN) as nodes in the thermosensory neural circuitry and indicate the opioid system within the POA is vital in regulating body temperate. In the present study we identify neurons projecting to the POA from PBN expressing the opioid peptides Dynorphin (Dyn) and Enkephalin (Enk). We determine that warm-activated PBN neuronal populations overlap with both Dyn and Enk expressing PBN populations. We demonstrate that Dyn and Enk expressing neurons are partially overlapping subsets of a glutamatergic population in the PBN. Using optogenetic approaches we selectively activate projections in the POA from PBN Dyn, Enk, and VGLUT2 expressing neurons. Our findings demonstrate that Dyn, Enk, and VGLUT2 expressing PBN neurons are critical for physiological and behavioral heat defense.

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Preoptic BRS3 neurons increase body temperature and heart rate via multiple pathways

10.1101/2021.03.04.433948 ◽

2021 ◽

Author(s):

Ramón A Pi&ntildeol ◽

Allison S Mogul ◽

Colleen K Hadley ◽

Atreyi Saha ◽

Chia Li ◽

...

Keyword(s):

Heart Rate ◽

Body Temperature ◽

Neural Circuits ◽

Preoptic Area ◽

Behavioral Responses ◽

Orphan Receptor ◽

Dorsomedial Hypothalamus ◽

Neuronal Populations ◽

Fine Tune

The preoptic area (POA) is a key region controlling body temperature (Tb), dictating thermogenic, cardiovascular, and behavioral responses to regulate Tb. Known POA neuronal populations reduce Tb when activated; a population that increases Tb upon activation has not yet been reported. We now identify bombesin-like receptor 3 (BRS3)-expressing POA (POABRS3) neurons as having this missing functionality. BRS3 is an orphan receptor that regulates energy and cardiovascular homeostasis, but the relevant neural circuits are incompletely understood. In mice, we demonstrate that POABRS3 neuronal activation increases Tb, heart rate, and blood pressure sympathetically, via projections to the paraventricular nucleus of the hypothalamus and dorsomedial hypothalamus. Acute POABRS3 inhibition reduces Tb. Long-term inactivation of POABRS3 neurons increased Tb variability with exaggerated Tb changes, overshooting both increases and decreases in Tb set point. BRS3 marks preoptic populations that regulate Tb and heart rate, contribute to cold-defense and fine-tune feedback control of Tb. These findings advance understanding of homeothermy, a defining feature of mammalian biology.

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An operant temperature sensory assay provides a means to assess thermal discrimination

Molecular Pain ◽

10.1177/17448069211013633 ◽

2021 ◽

Vol 17 ◽

pp. 174480692110136

Author(s):

Matthew Isaacson ◽

Mark A Hoon

Keyword(s):

Temperature Change ◽

Behavioral Responses ◽

Large Temperature ◽

Thermal Nociception ◽

Temperature Changes ◽

Neuronal Populations ◽

Rapid Temperature ◽

Thermal Stimuli ◽

The Brain ◽

Behavioral Assays

Mouse behavioral assays have proven useful for the study of thermosensation, helping to identify receptors and circuits responsible for the transduction of thermal stimuli and information relay to the brain. However, these methods typically rely on observation of behavioral responses to various temperature stimuli to infer sensory ability and are often unable to disambiguate innocuous thermosensation from thermal nociception or to study thermosensory circuitry which do not produce easily detectable innate behavioral responses. Here we demonstrate a new testing apparatus capable of delivering small, rapid temperature change stimuli to the mouse’s skin, permitting the use of operant conditioning to train mice to recognize and report temperature change. Using this assay, mice that were trained to detect a large temperature change were found to generalize this learning to distinguish much smaller temperature changes across the entire range of innocuous temperatures tested. Mice with ablated TRPV1 and TRPM8 neuronal populations had reduced ability to discriminate temperature differences in the warm (>35°C) and cool (<30°C) ranges, respectively. Furthermore, mice that were trained to recognize temperature changes in only the cool, TRPM8-mediated temperature range did not generalize this learning in the warm, TRPV1-mediated range (and vice versa), suggesting that thermosensory information from the TRPM8- and TRPV1-neuronal populations are perceptually distinct.

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Changes in Body Temperature and Sleep-Wakefulness After Intrapreoptic Injection of Methoxamine in Rats

Neural Plasticity ◽

10.1155/np.2003.267 ◽

2003 ◽

Vol 10 (4) ◽

pp. 267-278 ◽

Cited By ~ 7

Author(s):

Ra. Vetrivelan ◽

Hruda Nanda Mallick ◽

Velayudhan Mohan Kumar

Keyword(s):

Body Temperature ◽

Adrenergic Receptors ◽

Preoptic Area ◽

Major Change ◽

Medial Preoptic Area ◽

Adrenergic Agonist ◽

Temperature Changes ◽

Short Period ◽

Male Wistar Rats ◽

Higher Doses

Several pieces of evidence suggest that the noradrenergic afferents in the medial preoptic area produce sleep and hypothermia by acting onα1adrenergic receptors. On the other hand, in a few studies monitoring body temperature with a rectal probe, preoptic injection of theα1adrenergic agonist methoxamine produced contradictory changes in body temperature and sleep-wakefulness. Such contradictions call for the re-examination of methoxamine induced body temperature changes using a better technique like telemetric recording. In the present study, we monitored body temperature and sleep-wakefulness simultaneously after the micro-injection of 0.5, 1, and 2μmol methoxamine, into the medial preoptic area of adult male Wistar rats. Methoxamine injection produced hypothermia but no major change in sleep-wakefulness during the 3 hours after drug injection, except for a short period (15 min) of sleep after 120 min of injection. A short period of wakefulness, coinciding with the maximum fall in body temperature (30 min after injection) occurred when methoxamine was administered at higher doses. The results of this study indicate that 1 adrenergic receptors participate in preoptically mediated thermoregulatory measures that reduce body temperature. Hypothermia induced by methoxamine might have masked the hypnogenic action of this drug.

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Fine mapping* of the bovine solute carrier family 25, member 4 (SLC25A4) gene to BTA27q14-q15 by fluorescence in situ hybridization and radiation hybrid mapping

Animal Genetics ◽

10.1046/j.1365-2052.2002.t01-15-00886.x ◽

2002 ◽

Vol 33 (4) ◽

pp. 318-320

Author(s):

C. Drogemuller ◽

H. Kuiper ◽

G. Hauke ◽

J. L. Williams ◽

O. Distl

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Fine Mapping ◽

Radiation Hybrid ◽

Radiation Hybrid Mapping ◽

Solute Carrier Family ◽

Hybrid Mapping ◽

Solute Carrier

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Core body temperature changes after sauna exposition in healthy subjects

Medical and Biological Sciences ◽

10.2478/v10251-012-0042-6 ◽

2012 ◽

Vol 26 (2) ◽

Author(s):

Joanna Pawlak ◽

Paweł Zalewski ◽

Jacek J. Klawe ◽

Monika Zawadka ◽

Anna Bitner ◽

...

Keyword(s):

Body Temperature ◽

Healthy Subjects ◽

Core Body Temperature ◽

Temperature Changes ◽

Core Body

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Autosomal recessive congenital hereditary corneal dystrophy associated with a novel SLC4A11 mutation in two consanguineous Tunisian families

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-318204 ◽

2021 ◽

pp. bjophthalmol-2020-318204

Author(s):

Zohra Chibani ◽

Imen Zone Abid ◽

Peter Söderkvist ◽

Jamel Feki ◽

Mounira Hmani Aifa

Keyword(s):

Autosomal Recessive ◽

Corneal Transplantation ◽

Gene Mutations ◽

In Silico Analysis ◽

Corneal Dystrophy ◽

Solute Carrier Family ◽

Transporter Protein ◽

Bicarbonate Transporter ◽

Corneal Clouding ◽

Solute Carrier

BackgroundAutosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11).MethodsTo identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families.ResultsA novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements.ConclusionTo the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype–phenotype correlations.

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Slc7a11 Modulated by POU2F1 is Involved in Pigmentation in Rabbit

International Journal of Molecular Sciences ◽

10.3390/ijms20102493 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2493 ◽

Cited By ~ 4

Author(s):

Yang Chen ◽

Shuaishuai Hu ◽

Lin Mu ◽

Bohao Zhao ◽

Manman Wang ◽

...

Keyword(s):

Skin Color ◽

Site Directed Mutagenesis ◽

Molecular Regulation ◽

Luciferase Reporter ◽

Directed Mutagenesis ◽

Regulation Mechanism ◽

Solute Carrier Family ◽

Depth Analysis ◽

Solute Carrier ◽

Fur Color

Solute carrier family 7 member 11 (Slc7a11) is a cystine/glutamate xCT transporter that controls the production of pheomelanin pigment to change fur and skin color in animals. Previous studies have found that skin expression levels of Slc7a11 varied significantly with fur color in Rex rabbits. However, the molecular regulation mechanism of Slc7a11 in pigmentation is unknown. Here, rabbit melanocytes were first isolated and identified. The distribution and expression pattern of Slc7a11 was confirmed in skin from rabbits with different fur colors. Slc7a11 affected the expression of pigmentation related genes and thus affected melanogenesis. Meanwhile, Slc7a11 decreased melanocyte apoptosis, but inhibition of Slc7a11 enhanced apoptosis. Furthermore, the POU2F1 protein was found to bind to the −713 to −703 bp region of Slc7a11 promoter to inhibit its activity in a dual-luciferase reporter and site-directed mutagenesis assay. This study reveals the function of the Slc7a11 in melanogenesis and provides in-depth analysis of the mechanism of fur pigmentation.

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