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Slow inward currents (SICs) are known as excitatory events of neurons elicited by astrocytic glutamate via activation of extrasynaptic NMDA receptors. By using slice electrophysiology, we tried to provide evidence that SICs can elicit synaptic plasticity. Age dependence of SICs and their impact on synaptic plasticity was also investigated in both on murine and human cortical slices. It was found that SICs can induce a moderate synaptic plasticity, with features similar to spike timing-dependent plasticity. Overall SIC activity showed a clear decline with aging in humans and completely disappeared above a cutoff age. In conclusion, while SICs contribute to a form of astrocyte-dependent synaptic plasticity both in mice and humans, this plasticity is differentially affected by aging. Thus, SICs are likely to play an important role in age-dependent physiological and pathological alterations of synaptic plasticity.
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http://dx.doi.org/10.1111/acel.13939 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
Department of Neuroscience, The Scripps Research Institute, San Diego, CA 92037.
Microglia regulate neuronal circuit plasticity. Disrupting their homeostatic function has detrimental effects on neuronal circuit health. Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, including Alzheimer's disease (AD), with several microglial activation genes linked to increased risk for these conditions.
View Article and Find Full Text PDFJ Vis Exp
August 2025
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University;
Examining circadian synaptic plasticity requires housing mice under different lighting conditions (light/dark cycle, LD 12:12, and constant darkness, DD), providing access to running wheels, and sacrificing them at four defined time points within 24 h-at the beginning and middle of the day/subjective day and at the beginning and middle of the night/subjective night. Brains are then properly fixed for transmission electron microscopy (TEM). The barrel cortex, with its precise somatotopic organization, provides an ideal model for such analysis.
View Article and Find Full Text PDFHNO
September 2025
Tinnituszentrum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany Charitéplatz 1, 10117, Berlin, Deutschland.
Chronic tinnitus is a common symptom of the auditory system. Its pathophysiology remains incompletely understood, primarily due to its multifactorial etiology, which resembles that of other chronic conditions. As a result, effective clinical management requires interdisciplinary diagnostics and personalized therapeutic strategies.
View Article and Find Full Text PDFJ Cell Biol
November 2025
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Two major protein recycling pathways have emerged as key regulators of enduring forms of synaptic plasticity, such as long-term potentiation (LTP), yet how these pathways are recruited during plasticity is unknown. Phosphatidylinositol-3-phosphate (PI(3)P) is a key regulator of endosomal trafficking and alterations in this lipid have been linked to neurodegeneration. Here, using primary hippocampal neurons, we demonstrate dynamic PI(3)P synthesis during chemical induction of LTP (cLTP), which drives coordinate recruitment of the SNX17-Retriever and SNX27-Retromer pathways to endosomes and synaptic sites.
View Article and Find Full Text PDFJ Integr Neurosci
August 2025
Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 100853 Beijing, China.
Neurocognitive disorders represent a significant global health challenge and are characterized by progressive cognitive decline across conditions including Alzheimer's disease, mild cognitive impairment, and diabetes-related cognitive impairment. The hippocampus is essential for learning and memory and requires intact neuroplasticity to maintain cognitive function. Recent evidence has identified the brain insulin signaling pathway as a key regulator of hippocampal neuroplasticity through multiple cellular processes including synaptic plasticity, neurotransmitter regulation, and neuronal survival.
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