Quantal release of the principal excitatory neurotransmitter glutamate requires a mechanism for its transport into secretory vesicles. Within the brain, the complementary expression of vesicular glutamate transporters (VGLUTs) 1 and 2 accounts for the release of glutamate by all known excitatory neurons. We now report the identification of VGLUT3 and its expression by many cells generally considered to release a classical transmitter with properties very different from glutamate. Remarkably, subpopulations of inhibitory neurons as well as cholinergic interneurons, monoamine neurons, and glia express VGLUT3. The dendritic expression of VGLUT3 by particular neurons also indicates the potential for retrograde synaptic signaling. The distribution and subcellular location of VGLUT3 thus suggest novel modes of signaling by glutamate.
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http://dx.doi.org/10.1073/pnas.222546799 | DOI Listing |
Proc Natl Acad Sci U S A
December 2024
Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, Göttingen 37077, Germany.
Optical imaging access to nanometer-level protein distributions in intact tissue is a highly sought-after goal, as it would provide visualization in physiologically relevant contexts. Under the unfavorable signal-to-background conditions of increased absorption and scattering of the excitation and fluorescence light in the complex tissue sample, superresolution fluorescence microscopy methods are severely challenged in attaining precise localization of molecules. We reasoned that the typical use of a confocal detection pinhole in MINFLUX nanoscopy, suppressing background and providing optical sectioning, should facilitate the detection and resolution of single fluorophores even amid scattering and optically challenging tissue environments.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
Growth hormone (GH) has several metabolic effects, including a profound impact on glucose homeostasis. For example, GH oversecretion induces insulin resistance and increases the risk of developing diabetes mellitus. Here, we show that GH receptor (GHR) ablation in vesicular glutamate transporter 2 (VGLUT2)-expressing cells, which comprise a subgroup of glutamatergic neurons, led to a slight decrease in lean body mass without inducing changes in body adiposity.
View Article and Find Full Text PDFElife
December 2024
Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, United States.
Hypothalamic kisspeptin (Kiss1) neurons are vital for pubertal development and reproduction. Arcuate nucleus Kiss1 (Kiss1) neurons are responsible for the pulsatile release of gonadotropin-releasing hormone (GnRH). In females, the behavior of Kiss1 neurons, expressing Kiss1, neurokinin B (NKB), and dynorphin (Dyn), varies throughout the ovarian cycle.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Introduction: Progressive supranuclear palsy (PSP) is a devastating 4R tauopathy affecting motor functions and is often misdiagnosed/underdiagnosed due to a lack of specific biomarkers. Synaptic loss is an eminent feature of tauopathies including PSP. Novel synaptic positron emission tomography tracer UCB-J holds great potential for early diagnosis; however, there is a substantial knowledge gap in terms of the mechanism and the extent and nature of synaptic loss in PSP.
View Article and Find Full Text PDFBackground: Kisspeptin (KP) signaling in the brain is defined by the anatomical distribution of KP-producing neurons, their fibers, receptors, and connectivity. Technological advances have prompted a re-evaluation of these chemoanatomical aspects, originally studied in the early years after the discovery of KP and its receptor We have previously characterized(1) seven KP neuronal populations in the mouse brain at the mRNA level, including two novel populations, and examined their short-term response to gonadectomy.
Methods: In this study, we mapped KP fiber distribution in rats and mice using immunohistochemistry under intact and short- and long-term post-gonadectomy conditions.
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