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Stephen Liberles

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...
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...
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
Mark A Johnson, Lulu Tsai, Dheeraj S Roy, David H Valenzuela, Colleen Mosley, Angeliki Magklara, Stavros Lomvardas, Stephen D Liberles, Gilad Barnea
Some chemoreceptors of the trace amine-associated receptor (TAAR) family detect innately aversive odors and are proposed to activate hardwired olfactory circuits. However, the wiring of TAAR neurons, the regulatory mechanisms of Taar gene choice, and the subcellular localization of TAAR proteins remain unknown. Here, we reveal similarities between neurons expressing TAARs and odorant receptors (ORs), but also unexpected differences. Like ORs, TAARs seem to be monoallelically expressed and localized both in cilia, the site of odor detection, and in axons, where they may participate in guidance...
August 14, 2012: Proceedings of the National Academy of Sciences of the United States of America
David M Ferrero, Daniel Wacker, Miguel A Roque, Maude W Baldwin, Raymond C Stevens, Stephen D Liberles
Trace amine-associated receptors (TAARs) are vertebrate olfactory receptors. However, ligand recognition properties of TAARs remain poorly understood, as most are "orphan receptors" without known agonists. Here, we identify the first ligands for many rodent TAARs and classify these receptors into two subfamilies based on the phylogeny and binding preference for primary or tertiary amines. Some mouse and rat orthologs have similar response profiles, although independent Taar7 gene expansions led to highly related receptors with altered ligand specificities...
July 20, 2012: ACS Chemical Biology
David M Ferrero, Jamie K Lemon, Daniela Fluegge, Stan L Pashkovski, Wayne J Korzan, Sandeep Robert Datta, Marc Spehr, Markus Fendt, Stephen D Liberles
Predator-prey relationships provide a classic paradigm for the study of innate animal behavior. Odors from carnivores elicit stereotyped fear and avoidance responses in rodents, although sensory mechanisms involved are largely unknown. Here, we identified a chemical produced by predators that activates a mouse olfactory receptor and produces an innate behavioral response. We purified this predator cue from bobcat urine and identified it to be a biogenic amine, 2-phenylethylamine. Quantitative HPLC analysis across 38 mammalian species indicates enriched 2-phenylethylamine production by numerous carnivores, with some producing >3,000-fold more than herbivores examined...
July 5, 2011: Proceedings of the National Academy of Sciences of the United States of America
France Denoeud, Simon Henriet, Sutada Mungpakdee, Jean-Marc Aury, Corinne Da Silva, Henner Brinkmann, Jana Mikhaleva, Lisbeth Charlotte Olsen, Claire Jubin, Cristian Cañestro, Jean-Marie Bouquet, Gemma Danks, Julie Poulain, Coen Campsteijn, Marcin Adamski, Ismael Cross, Fekadu Yadetie, Matthieu Muffato, Alexandra Louis, Stephen Butcher, Georgia Tsagkogeorga, Anke Konrad, Sarabdeep Singh, Marit Flo Jensen, Evelyne Huynh Cong, Helen Eikeseth-Otteraa, Benjamin Noel, Véronique Anthouard, Betina M Porcel, Rym Kachouri-Lafond, Atsuo Nishino, Matteo Ugolini, Pascal Chourrout, Hiroki Nishida, Rein Aasland, Snehalata Huzurbazar, Eric Westhof, Frédéric Delsuc, Hans Lehrach, Richard Reinhardt, Jean Weissenbach, Scott W Roy, François Artiguenave, John H Postlethwait, J Robert Manak, Eric M Thompson, Olivier Jaillon, Louis Du Pasquier, Pierre Boudinot, David A Liberles, Jean-Nicolas Volff, Hervé Philippe, Boris Lenhard, Hugues Roest Crollius, Patrick Wincker, Daniel Chourrout
Genomes of animals as different as sponges and humans show conservation of global architecture. Here we show that multiple genomic features including transposon diversity, developmental gene repertoire, physical gene order, and intron-exon organization are shattered in the tunicate Oikopleura, belonging to the sister group of vertebrates and retaining chordate morphology. Ancestral architecture of animal genomes can be deeply modified and may therefore be largely nonadaptive. This rapidly evolving animal lineage thus offers unique perspectives on the level of genome plasticity...
December 3, 2010: Science
David M Ferrero, Stephen D Liberles
The scents of mammals are complex blends of natural products that reveal a wealth of individual information. Many mammals can decipher these scent codes to discern the gender, age, endocrine status, social status, and genotype of conspecifics using dedicated sensory receptors in their olfactory system. Among these social odors are pheromones, chemicals that trigger innate behaviors and physiological responses. Here, we review classes of mammal-derived natural products that influence behavior through activation of the olfactory system...
January 2010: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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