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The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction indicated by a peripheral visual stimulus while maintaining fixation at the center, and report the direction of the cue by performing a saccadic eye movement into the same direction following a delay.
View Article and Find Full Text PDFKeratinocyte-derived extracellular vesicles in painful diabetic neuropathy.
Neurobiol Pain
December 2024
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Painful diabetic neuropathy (PDN) is a challenging complication of diabetes with patients experiencing a painful and burning sensation in their extremities. Existing treatments provide limited relief without addressing the underlying mechanisms of the disease. PDN involves the gradual degeneration of nerve fibers in the skin.
View Article and Find Full Text PDFThe interaction of tPA with NMDAR1 drives neuroinflammation and neurodegeneration in α-synuclein-mediated neurotoxicity.
J Neuroinflammation
January 2025
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice.
View Article and Find Full Text PDFNde1 Promotes Lis1 Binding to Full-Length Autoinhibited Human Dynein-1.
bioRxiv
December 2024
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06511, USA.
Cytoplasmic dynein-1 (dynein) is the primary motor for the retrograde transport of intracellular cargoes along microtubules. The activation of the dynein transport machinery requires the opening of its autoinhibited Phi conformation by Lis1 and Nde1/Ndel1, but the underlying mechanism remains unclear. Using biochemical reconstitution and cryo-electron microscopy, we show that Nde1 significantly enhances Lis1 binding to autoinhibited dynein and facilitates the opening of Phi.
View Article and Find Full Text PDFAn intra-brainstem circuitry for pain-induced inhibition of itch.
Neuroscience
January 2025
Center for Neuroscience, Indian Institute of Science, Bengaluru 560012, India. Electronic address:
Pain and itch are unpleasant and distinct sensations that give rise to behaviors such as reflexive withdrawal and scratching in humans and mice. Interestingly, it has been observed that pain modulate itch through the neural circuits housed in the brain and spinal cord. However, we are yet to fully understand the identities of, and mechanisms by which specific neural circuits mediate pain-induced modulation of itch.
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