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Lou, Shan

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Lou, Shan
Author's Publications: search.filters.isAuthorOfPublication.80458114-38a5-465f-9f84-23f9e7dcc2d1

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    DEVELOPMENT AND FUNCTIONS OF C-LOW-THRESHOLD MECHANORECEPTORS
    (2013-10-08) Lou, Shan; Ma, Qiufu; Segal, Rosalind; Dong, Xinzhong; Gu, Chenghua; Bean, Bruce; Macklis, Jeffery; Woolf, Clifford
    Somatosensory neurons are essential for detecting diverse environmental stimuli, thus critical for survival of mammals. In order to achieve sensory modality specificity, many somatosensory subtypes emerge with various receptor and ion channel expression, as well as terminal morphologies. How the somatosensory system achieves such a high variety of neuronal subtypes is unknown. In this thesis, I used a newly discovered subtype, VGLUT3-expressing unmyelinated low-threshold mechanoreceptors (C-LTMRs), as a model to try to answer this question. C-LTMRs have been proposed to play a role in pleasant touch in humans or pain in mice. Previously, our lab has identified the Runt domain transcriptional factor Runx1 to be pivotal for the development of a cohort of sensory neurons such as pain related nociceptors, thermal receptors, as well as itch related pruriceptors. Here I found that Runx1 is also required to establish all known features associated with C-LTMRs. In search of the mechanism of how Runx1 controls C-LTMR development, I found that the zinc finger protein Zfp521 is predominantly expressed in C-LTMRs and its expression is Runx1 dependent. By generating and analyzing Zfp521 conditional knock out animals, I found Zfp521 is required for part of C-LTMR molecular identities and nerve terminal morphologies. Our studies suggest that Runx1 acts through Zfp521-dependent and Zfp521-independent pathways to specify C-LTMR identities. To study C-LTMR functions, we performed a series of behavioral analysis and found the loss of VGLUT3 and mechanosensitivities in C-LTMRs does not markedly affect acute or chronic mechanical pain measured from the hind paws, which argues against the proposed role of VGLUT3 in C-LTMRs in mediating mechanical pain in mice. In the future, we will continue to use our mutant mice to study physiological functions of C-LTMRs.
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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.