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Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder.
J Med Chem
January 2025
Department of Pharmaceutical Sciences, College of Health and Human Sciences, North Dakota State University, Fargo, North Dakota 58105, United States.
Treatment-resistant depression responds quickly to ketamine. As an -methyl-d-aspartate receptor (NMDAR) antagonist, ketamine may affect prefrontal cortex (PFC) neurons. Recent investigations reveal that the ()-enantiomer is the most effective and least abuseable antidepressant.
View Article and Find Full Text PDFRapid lightsheet fluorescence imaging of whole Drosophila brains at nanoscale resolution by potassium acrylate-based expansion microscopy.
Nat Commun
December 2024
Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan.
Taking advantage of the good mechanical strength of expanded Drosophila brains and to tackle their relatively large size that can complicate imaging, we apply potassium (poly)acrylate-based hydrogels for expansion microscopy (ExM), resulting in a 40x plus increased resolution of transgenic fluorescent proteins preserved by glutaraldehyde fixation in the nervous system. Large-volume ExM is realized by using an axicon-based Bessel lightsheet microscope, featuring gentle multi-color fluorophore excitation and intrinsic optical sectioning capability, enabling visualization of Tm5a neurites and L3 lamina neurons with photoreceptors in the optic lobe. We also image nanometer-sized dopaminergic neurons across the same intact iteratively expanded Drosophila brain, enabling us to measure the 3D expansion ratio.
View Article and Find Full Text PDFMinimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release.
Nat Commun
December 2024
Nanobiology Institute, Yale University, West Haven, CT, USA.
Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic calcium influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically relevant conditions to delineate the minimal protein machinery sufficient to account for various modes of calcium-triggered vesicle fusion dynamics.
View Article and Find Full Text PDFDivergent Effects of Ketamine and the Serotoninergic Psychedelic 2,5-Dimethoxy-4-Iodoamphetamine on Hippocampal Plasticity and Metaplasticity.
Psychedelic Med (New Rochelle)
September 2024
Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53706.
Introduction: Serotonergic psychedelics and ketamine produce rapid and long-lasting symptomatic relief in multiple psychiatric disorders. Evidence suggests that despite having distinct molecular targets, both drugs may exert therapeutic benefit via their pro-neuroplastic effects. Following treatment with ketamine or serotonergic psychedelics, patients are reported to be more open to behavioral change, which is leveraged for psychotherapy-assisted reframing of narratives of the self.
View Article and Find Full Text PDFA novel image segmentation method based on spatial autocorrelation identifies A-type potassium channel clusters in the thalamus.
Elife
December 2024
Lendület Laboratory of Thalamus Research, HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Unsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here, we propose a spatial autocorrelation method based on Local Moran's coefficient to differentiate signal, background, and noise in any type of image.
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