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Stephen Liberles

Jessica M Adams, Hongjuan Pei, Darleen A Sandoval, Randy J Seeley, Rui B Chang, Stephen D Liberles, David P Olson
Glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved weight loss drugs. Despite their widespread use, the sites of action through which GLP-1R agonists (GLP1RAs) impact appetite and body weight are still not fully understood. Here, we determined whether GLP-1Rs in either GABAergic or glutamatergic neurons are necessary for the acute and chronic effects of the GLP1RA liraglutide on food intake, visceral illness, body weight and neural network activation. We found that mice lacking GLP-1Rs in vGAT -expressing GABAergic neurons responded identically to controls in all parameters measured, whereas deletion of GLP-1Rs in vGlut2 -expressing glutamatergic neurons eliminated liraglutide-induced weight loss and visceral illness and severely attenuated its effects on feeding...
May 18, 2018: Diabetes
Pankaj Baral, Benjamin D Umans, Lu Li, Antonia Wallrapp, Meghna Bist, Talia Kirschbaum, Yibing Wei, Yan Zhou, Vijay K Kuchroo, Patrick R Burkett, Bryan G Yipp, Stephen D Liberles, Isaac M Chiu
Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1+ nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1+ -neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung γδ T cell numbers, which are necessary for immunity...
May 2018: Nature Medicine
Russell A Hermansen, Benjamin P Oswald, Stormy Knight, Stephen D Shank, David Northover, Katharine L Korunes, Stephen N Michel, David A Liberles
With the large collections of gene and genome sequences, there is a need to generate curated comparative genomic databases that enable interpretation of results in an evolutionary context. Such resources can facilitate an understanding of the co-evolution of genes in the context of a genome mapped onto a phylogeny, of a protein structure, and of interactions within a pathway. A phylogenetically indexed gene family database, the adaptive evolution database (TAED), is presented that organizes gene families and their evolutionary histories in a species tree context...
August 2017: Journal of Molecular Evolution
Keiko Nonomura, Seung-Hyun Woo, Rui B Chang, Astrid Gillich, Zhaozhu Qiu, Allain G Francisco, Sanjeev S Ranade, Stephen D Liberles, Ardem Patapoutian
Respiratory dysfunction is a notorious cause of perinatal mortality in infants and sleep apnoea in adults, but the mechanisms of respiratory control are not clearly understood. Mechanical signals transduced by airway-innervating sensory neurons control respiration; however, the physiological significance and molecular mechanisms of these signals remain obscured. Here we show that global and sensory neuron-specific ablation of the mechanically activated ion channel Piezo2 causes respiratory distress and death in newborn mice...
January 12, 2017: Nature
Shan Lou, Yoav Adam, Eli N Weinstein, Erika Williams, Katherine Williams, Vicente Parot, Nikita Kavokine, Stephen Liberles, Linda Madisen, Hongkui Zeng, Adam E Cohen
Recent advances in optogenetics have enabled simultaneous optical perturbation and optical readout of membrane potential in diverse cell types. Here, we develop and characterize a Cre-dependent transgenic Optopatch2 mouse line that we call Floxopatch. The animals expressed a blue-shifted channelrhodopsin, CheRiff, and a near infrared Archaerhodopsin-derived voltage indicator, QuasAr2, via targeted knock-in at the rosa26 locus. In Optopatch-expressing animals, we tested for overall health, genetically targeted expression, and function of the optogenetic components...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Erika K Williams, Rui B Chang, David E Strochlic, Benjamin D Umans, Bradford B Lowell, Stephen D Liberles
Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate the molecular diversity of vagal sensory neurons and their roles in sensing gastrointestinal inputs. Genetic approaches allowed targeted investigation of gut-to-brain afferents involved in homeostatic responses to ingested nutrients (GPR65 neurons) and mechanical distension of the stomach and intestine (GLP1R neurons)...
June 30, 2016: Cell
Lisa Stowers, Stephen D Liberles
A single sensory cue can evoke different behaviors that vary by recipient. Responses may be influenced by sex, internal state, experience, genotype, and coincident environmental stimuli. Pheromones are powerful inducers of mouse behavior, yet pheromone responses are not always stereotyped. For example, male and female mice respond differently to sex pheromones while mothers and virgin females respond differently to pup cues. Here, we review the origins of variability in responses to reproductive pheromones...
June 2016: Current Opinion in Neurobiology
Qian Li, Yaw Tachie-Baffour, Zhikai Liu, Maude W Baldwin, Andrew C Kruse, Stephen D Liberles
Biogenic amines are important signaling molecules, and the structural basis for their recognition by G Protein-Coupled Receptors (GPCRs) is well understood. Amines are also potent odors, with some activating olfactory trace amine-associated receptors (TAARs). Here, we report that teleost TAARs evolved a new way to recognize amines in a non-classical orientation. Chemical screens de-orphaned eleven zebrafish TAARs, with agonists including serotonin, histamine, tryptamine, 2-phenylethylamine, putrescine, and agmatine...
October 31, 2015: ELife
Lucas Vicuña, David E Strochlic, Alban Latremoliere, Kiran Kumar Bali, Manuela Simonetti, Dewi Husainie, Sandra Prokosch, Priscilla Riva, Robert S Griffin, Christian Njoo, Stefanie Gehrig, Marcus A Mall, Bernd Arnold, Marshall Devor, Clifford J Woolf, Stephen D Liberles, Michael Costigan, Rohini Kuner
Neuropathic pain is a major, intractable clinical problem and its pathophysiology is not well understood. Although recent gene expression profiling studies have enabled the identification of novel targets for pain therapy, classical study designs provide unclear results owing to the differential expression of hundreds of genes across sham and nerve-injured groups, which can be difficult to validate, particularly with respect to the specificity of pain modulation. To circumvent this, we used two outbred lines of rats, which are genetically similar except for being genetically segregated as a result of selective breeding for differences in neuropathic pain hypersensitivity...
May 2015: Nature Medicine
Isaac M Chiu, Lee B Barrett, Erika K Williams, David E Strochlic, Seungkyu Lee, Andy D Weyer, Shan Lou, Gregory Bryman, David P Roberson, Nader Ghasemlou, Cara Piccoli, Ezgi Ahat, Victor Wang, Enrique J Cobos, Cheryl L Stucky, Qiufu Ma, Stephen D Liberles, Clifford Woolf
No abstract text is available yet for this article.
2015: ELife
Qian Li, Stephen D Liberles
Sensory cues that predict reward or punishment are fundamental drivers of animal behavior. For example, attractive odors of palatable food or a potential mate predict reward, while aversive odors of pathogen-laced food or a predator predict punishment. Aversive and attractive odors can be detected by intermingled sensory neurons that express highly related olfactory receptors and display similar central projections. These findings raise basic questions of how innate odor valence is extracted from olfactory circuits, how such circuits are developmentally endowed and modulated by state, and how innate and learned odor responses are related...
February 2, 2015: Current Biology: CB
Stephen D Liberles
Trace amine-associated receptors (TAARs) are G Protein-Coupled Receptors that function as vertebrate olfactory receptors. Like odorant receptors, TAARs constitute an ever-evolving sensory subsystem, with individual TAARs recognizing particular chemicals and some evoking stereotyped behaviors. Several TAARs mediate aversion or attraction towards volatile amines that include the mouse odor trimethylamine, the predator odor 2-phenylethylamine, and the death-associated odor cadaverine. TAAR-expressing sensory neurons achieve monoallelic receptor expression, use canonical olfactory signaling molecules, and target a dedicated olfactory bulb region...
October 2015: Current Opinion in Neurobiology
Isaac M Chiu, Lee B Barrett, Erika K Williams, David E Strochlic, Seungkyu Lee, Andy D Weyer, Shan Lou, Gregory S Bryman, David P Roberson, Nader Ghasemlou, Cara Piccoli, Ezgi Ahat, Victor Wang, Enrique J Cobos, Cheryl L Stucky, Qiufu Ma, Stephen D Liberles, Clifford J Woolf
The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4(+)SNS-Cre/TdTomato(+), 2) IB4(-)SNS-Cre/TdTomato(+), and 3) Parv-Cre/TdTomato(+) cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons...
December 19, 2014: ELife
Maude W Baldwin, Yasuka Toda, Tomoya Nakagita, Mary J O'Connell, Kirk C Klasing, Takumi Misaka, Scott V Edwards, Stephen D Liberles
Sensory systems define an animal's capacity for perception and can evolve to promote survival in new environmental niches. We have uncovered a noncanonical mechanism for sweet taste perception that evolved in hummingbirds since their divergence from insectivorous swifts, their closest relatives. We observed the widespread absence in birds of an essential subunit (T1R2) of the only known vertebrate sweet receptor, raising questions about how specialized nectar feeders such as hummingbirds sense sugars. Receptor expression studies revealed that the ancestral umami receptor (the T1R1-T1R3 heterodimer) was repurposed in hummingbirds to function as a carbohydrate receptor...
August 22, 2014: Science
Michael J Krashes, Bhavik P Shah, Joseph C Madara, David P Olson, David E Strochlic, Alastair S Garfield, Linh Vong, Hongjuan Pei, Mitsuko Watabe-Uchida, Naoshige Uchida, Stephen D Liberles, Bradford B Lowell
Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity...
March 13, 2014: Nature
Ashiq Hussain, Luis R Saraiva, David M Ferrero, Gaurav Ahuja, Venkatesh S Krishna, Stephen D Liberles, Sigrun I Korsching
Carrion smell is strongly repugnant to humans and triggers distinct innate behaviors in many other species. This smell is mainly carried by two small aliphatic diamines, putrescine and cadaverine, which are generated by bacterial decarboxylation of the basic amino acids ornithine and lysine. Depending on the species, these diamines may also serve as feeding attractants, oviposition attractants, or social cues. Behavioral responses to diamines have not been investigated in zebrafish, a powerful model system for studying vertebrate olfaction...
November 26, 2013: Proceedings of the National Academy of Sciences of the United States of America
David M Ferrero, Lisa M Moeller, Takuya Osakada, Nao Horio, Qian Li, Dheeraj S Roy, Annika Cichy, Marc Spehr, Kazushige Touhara, Stephen D Liberles
Animals display a repertoire of different social behaviours. Appropriate behavioural responses depend on sensory input received during social interactions. In mice, social behaviour is driven by pheromones, chemical signals that encode information related to age, sex and physiological state. However, although mice show different social behaviours towards adults, juveniles and neonates, sensory cues that enable specific recognition of juvenile mice are unknown. Here we describe a juvenile pheromone produced by young mice before puberty, termed exocrine-gland secreting peptide 22 (ESP22)...
October 17, 2013: Nature
Stephen D Liberles
Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins...
2014: Annual Review of Physiology
David M Ferrero, Stephen D Liberles
Male and female mice behave differently when encountering a male. A recent study identifies progesterone receptor-expressing neurons in the hypothalamus that are required for sexual behavior and male aggression. These findings provide insight into how neural circuits control sexually dimorphic behaviors.
July 22, 2013: Current Biology: CB
Qian Li, Wayne J Korzan, David M Ferrero, Rui B Chang, Dheeraj S Roy, Mélanie Buchi, Jamie K Lemon, Angeldeep W Kaur, Lisa Stowers, Markus Fendt, Stephen D Liberles
BACKGROUND: Rodents use olfactory cues for species-specific behaviors. For example, mice emit odors to attract mates of the same species, but not competitors of closely related species. This implies rapid evolution of olfactory signaling, although odors and chemosensory receptors involved are unknown. RESULTS: Here, we identify a mouse chemosignal, trimethylamine, and its olfactory receptor, trace amine-associated receptor 5 (TAAR5), to be involved in species-specific social communication...
January 7, 2013: Current Biology: CB
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