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Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.
Stem Cell Reports
January 2025
Research Center, Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan; Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan. Electronic address:
We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1 ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays.
View Article and Find Full Text PDFBackground: Diabetes is known to cause cognitive impairments and synaptic dysfunction. This study investigates the effects of (EO), (CT), Vitamin C, and metformin on cognitive function and synaptic density (SYN) in diabetic rats. This work aims to evaluate the impact of various treatments on spatial learning, memory, and SYN in a diabetic rat model.
View Article and Find Full Text PDFEpigenetics in Learning and Memory.
Subcell Biochem
January 2025
Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences (ICB), Universidad Andres Bello, Santiago, Chile.
In animals, memory formation and recall are essential for their survival and for adaptations to a complex and often dynamically changing environment. During memory formation, experiences prompt the activation of a selected and sparse population of cells (engram cells) that undergo persistent physical and/or chemical changes allowing long-term memory formation, which can last for decades. Over the past few decades, important progress has been made on elucidating signaling mechanisms by which synaptic transmission leads to the induction of activity-dependent gene regulation programs during the different phases of learning (acquisition, consolidation, and recall).
View Article and Find Full Text PDFAging disrupts the link between network centrality and functional properties of prefrontal neurons during memory-guided behavior.
Commun Biol
January 2025
Neuroscience & Mental Health, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore.
The prefrontal cortex (PFC) is vital for higher cognitive functions and displays neuronal heterogeneity, with neuronal activity varying significantly across individual neurons. Using calcium imaging in the medial PFC (mPFC) of mice, we investigate whether differences in degree centrality-a measure of connectivity strength within local circuits-could explain this neuronal diversity and its functional implications. In young adults, neurons with high degree centrality, inferred from resting-state activity, exhibit reliable and stable action-plan selectivity during memory-guided tasks, suggesting that connectivity strength is closely linked to functional heterogeneity.
View Article and Find Full Text PDFReconstitution of synaptic junctions orchestrated by teneurin-latrophilin complexes.
Science
January 2025
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Synapses are organized by trans-synaptic adhesion molecules that coordinate assembly of pre- and postsynaptic specializations, which, in turn, are composed of scaffolding proteins forming liquid-liquid phase-separated condensates. Presynaptic teneurins mediate excitatory synapse organization by binding to postsynaptic latrophilins; however, the mechanism of action of teneurins, driven by extracellular domains evolutionarily derived from bacterial toxins, remains unclear. In this work, we show that only the intracellular sequence, a dimerization sequence, and extracellular bacterial toxin-derived latrophilin-binding domains of Teneurin-3 are required for synapse organization, suggesting that teneurin-induced latrophilin clustering mediates synaptogenesis.
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