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Strochlic, David E.

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Strochlic

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David E.

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Strochlic, David E.
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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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    Molecular and Genetic Analysis of the Vagus Nerve
    (2015-05-13) Strochlic, David E.; Majzoub, Joseph; Dymecki, Susan; Ginty, David; Barnea, Gilad
    The vagus nerve serves as a primary neural link between the brain and internal organs, detecting a variety of physiological stimuli and controlling a range of autonomic functions essential to homeostatic regulation. However, despite its fundamental importance, little is known about the repertoire of sensory mechanisms residing in vagal afferents, the cellular logic of information coding within the vagus nerve, and the central representation of internal physiological states. To dissect the neural circuits underlying viscerosensation, we adopted a genome-guided strategy to classify vagal sensory neurons based on G-protein-coupled receptor (GPCR) expression. We identified 5 principal cell types and obtained genetic access to these neurons in vivo using GPCR-ires-cre mouse strains. Using a combination of approaches that support cell-type specific analysis, we investigated the anatomical projections, response profiles, and physiological function of discrete vagal sensory subtypes. Within the respiratory system, we identified two vagal sensory populations that exert powerful and opposing effects on breathing. P2ry1- and Npy2r-expressing neurons innervate distinct anatomical structures in the lung and send projections to different brainstem targets. Npy2r neurons are largely slow-conducting C fibers while P2ry1 neurons are fast conducting A fibers. Optogenetic activation of Npy2r neurons induces rapid and shallow breathing whereas activating P2ry1 neurons acutely silences respiration, trapping animals in exhalation. Furthermore, activating P2ry1 neurons had no effect on heart rate or gastric pressure, other autonomic functions under vagal control. Thus, the vagus nerve contains intermingled sensory neurons constituting genetically definable labeled lines with different anatomical connections and physiological roles.
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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