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Liberles, Stephen

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Liberles

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Stephen

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Liberles, Stephen
Author's Publications: search.filters.isAuthorOfPublication.748c68fa-0dba-46c9-8788-e257d1a2e314

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Now showing 1 - 8 of 8
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    A juvenile mouse pheromone inhibits sexual behavior through the vomeronasal system
    (2013) Ferrero, David M.; Moeller, Lisa M.; Osakada, Takuya; Horio, Nao; Li, Qian; Roy, Dheeraj S.; Cichy, Annika; Spehr, Marc; Touhara, Kazushige; Liberles, Stephen
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    A Novel Excitatory Paraventricular Nucleus to AgRP Neuron Circuit that Drives Hunger
    (2014) Krashes, Michael J.; Shah, Bhavik P.; Madara, Joseph; Olson, David P.; Strochlic, David E.; Garfield, Alastair S.; Vong, Linh; Pei, Hongjuan; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Liberles, Stephen; Lowel, Bradford B.
    Summary 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 its control. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake1-5. Consistent with their obligatory role in regulating appetite, genetic ablation or pharmacogenetic inhibition of AgRP neurons decreases feeding3,6,7. Excitatory input to AgRP neurons is key in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric state-dependent synaptic plasticity8-10. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing Thyrotropin-releasing hormone (TRH) and Pituitary adenylate cyclase-activating polypeptide (PACAP). Pharmaco-genetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.
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    Non-classical amine recognition evolved in a large clade of olfactory receptors
    (eLife Sciences Publications, Ltd, 2015) Li, Qian; Tachie-Baffour, Yaw; Liu, Zhikai; Baldwin, Maude Wheeler; Kruse, Andrew; Liberles, Stephen
    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. Receptors from different clades contact ligands through aspartates on transmembrane α-helices III (canonical Asp3.32) or V (non-canonical Asp5.42), and diamine receptors contain both aspartates. Non-classical monoamine recognition evolved in two steps: an ancestral TAAR acquired Asp5.42, gaining diamine sensitivity, and subsequently lost Asp3.32. Through this transformation, the fish olfactory system dramatically expanded its capacity to detect amines, ecologically significant aquatic odors. The evolution of a second, alternative solution for amine detection by olfactory receptors highlights the tremendous structural versatility intrinsic to GPCRs. DOI: http://dx.doi.org/10.7554/eLife.10441.001
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    Evolution of sweet taste perception in hummingbirds by transformation of the ancestral umami receptor
    (American Association for the Advancement of Science (AAAS), 2014) Baldwin, Maude Wheeler; Toda, Y.; Nakagita, T.; O'Connell, Mary J.; Klasing, Kirk C.; Misaka, T.; Edwards, Scott; Liberles, Stephen
    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. Furthermore, the molecular recognition properties of T1R1-T1R3 guided taste behavior in captive and wild hummingbirds. We propose that changing taste receptor function enabled hummingbirds to perceive and use nectar, facilitating the massive radiation of hummingbird species.
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    The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell-derived leukocyte elastase
    (2015) Vicuña, Lucas; Strochlic, David E.; Latremoliere, Alban; Bali, Kiran Kumar; Simonetti, Manuela; Husainie, Dewi; Prokosch, Sandra; Riva, Priscilla; Griffin, Robert S.; Njoo, Christian; Gehrig, Stefanie; Mall, Marcus A.; Arnold, Bernd; Devor, Marshall; Woolf, Clifford; Liberles, Stephen; Costigan, Michael; Kuner, Rohini
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    Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity
    (eLife Sciences Publications, Ltd, 2014) Chiu, Isaac; Barrett, Lee; Williams, Erika; Strochlic, David E.; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Greg; Roberson, David; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen; Woolf, Clifford
    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. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001
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    Genetically Targeted All-Optical Electrophysiology with a Transgenic Cre-Dependent Optopatch Mouse
    (Society for Neuroscience, 2016) Lou, Shan; Adam, Yoav; Weinstein, Eli; Williams, E.; Williams, K.; Parot, Vicente; Kavokine, N.; Liberles, Stephen; Madisen, L.; Zeng, H.; Cohen, Adam
    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. In offspring of Floxopatch mice crossed with a variety of Cre driver lines, we observed spontaneous and optically evoked activity in vitro in acute brain slices and in vivo in somatosensory ganglia. Cell-type-specific expression allowed classification and characterization of neuronal subtypes based ontheir firing patterns. The Floxopatch mouse line is a usefultool for fast and sensitive characterization of neural activity in genetically specified cell types in intact tissue.
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    Hunger Enhances Food-Odour Attraction Through a Neuropeptide Y Spotlight
    (Springer Science and Business Media LLC, 2021-03-03) Horio, Nao; Liberles, Stephen