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Browsing by Author "Stebbins, Katelyn"

Now showing 1 - 3 of 3
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    Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and perturbs normal neuroendocrine stress axis function
    Ma, Manxiu; Brunal, Alyssa A.; Clark, Kareem C.; Studtmann, Carleigh; Stebbins, Katelyn; Higashijima, Shin-ichi; Pan, Y. Albert (Frontiers, 2023-02-16)
    The corticotropin-releasing hormone (CRH)-expressing neurons in the hypothalamus are critical regulators of the neuroendocrine stress response pathway, known as the hypothalamic-pituitary-adrenal (HPA) axis. As developmental vulnerabilities of CRH neurons contribute to stress-associated neurological and behavioral dysfunctions, it is critical to identify the mechanisms underlying normal and abnormal CRH neuron development. Using zebrafish, we identified Down syndrome cell adhesion molecule like-1 (dscaml1) as an integral mediator of CRH neuron development and necessary for establishing normal stress axis function. In dscaml1 mutant animals, hypothalamic CRH neurons had higher crhb (the CRH homolog in zebrafish) expression, increased cell number, and reduced cell death compared to wild-type controls. Physiologically, dscaml1 mutant animals had higher baseline stress hormone (cortisol) levels and attenuated responses to acute stressors. Together, these findings identify dscaml1 as an essential factor for stress axis development and suggest that HPA axis dysregulation may contribute to the etiology of human DSCAML1- linked neuropsychiatric disorders.
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    Parkinson’s Disease Tremor Detection in the Wild Using Wearable Accelerometers
    San-Segundo, Rubén; Zhang, Ada; Cebulla, Alexander; Panev, Stanislav; Tabor, Griffin; Stebbins, Katelyn; Massa, Robyn E.; Whitford, Andrew; de la Torre, Fernando; Hodgins, Jessica (MDPI, 2020-10-14)
    Continuous in-home monitoring of Parkinson’s Disease (PD) symptoms might allow improvements in assessment of disease progression and treatment effects. As a first step towards this goal, we evaluate the feasibility of a wrist-worn wearable accelerometer system to detect PD tremor in the wild (uncontrolled scenarios). We evaluate the performance of several feature sets and classification algorithms for robust PD tremor detection in laboratory and wild settings. We report results for both laboratory data with accurate labels and wild data with weak labels. The best performance was obtained using a combination of a pre-processing module to extract information from the tremor spectrum (based on non-negative factorization) and a deep neural network for learning relevant features and detecting tremor segments. We show how the proposed method is able to predict patient self-report measures, and we propose a new metric for monitoring PD tremor (i.e., percentage of tremor over long periods of time), which may be easier to estimate the start and end time points of each tremor event while still providing clinically useful information.
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    Sonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamus
    Somaiya, Rachana Deven; Stebbins, Katelyn; Gingrich, Ellen C.; Xie, Hehuang; Campbell, John N.; Garcia, A. Denise R.; Fox, Michael A. (Elife Sciences, 2022-11)
    Axons of retinal ganglion cells (RGCs) play critical roles in the development of inhibitory circuits in visual thalamus. We previously reported that RGC axons signal astrocytes to induce the expression of fibroblast growth factor 15 (FGF15), a motogen required for GABAergic interneuron migration into visual thalamus. However, how retinal axons induce thalamic astrocytes to generate Fgf15 and influence interneuron migration remains unknown. Here, we demonstrate that impairing RGC activity had little impact on interneuron recruitment into mouse visual thalamus. Instead, our data show that retinal-derived sonic hedgehog (SHH) is essential for interneuron recruitment. Specifically, we show that thalamus-projecting RGCs express SHH and thalamic astrocytes generate downstream components of SHH signaling. Deletion of RGC-derived SHH leads to a significant decrease in Fgf15 expression, as well as in the percentage of interneurons recruited into visual thalamus. Overall, our findings identify a morphogen-dependent neuron-astrocyte signaling mechanism essential for the migration of thalamic interneurons.