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One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation and long-term depression, respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by long-term potentiation and long-term depression, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity. Read the Editorial Highlight for this article on page 788. Cover Image for this issue: doi: 10.1111/jnc.13815.
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http://dx.doi.org/10.1111/jnc.14107 | DOI Listing |
Acta Neuropathol Commun
September 2025
Department of Biomedical and Clinical Sciences and Department of Clinical Pathology, Linköping University, 58185, Linköping, Sweden.
Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, 44115, USA.
Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons.
View Article and Find Full Text PDFNeurobiol Dis
September 2025
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi 563000, Guizhou, PR China; Key Laboratory of Brain Function and Brain Disease Prevention and Treatment of Guizhou Province, Zunyi 563000, Guizhou, PR China; The Collaborative Innovation Center of Tis
Lactylation is a novel post-translational modification (PTM) mediated by lactate, which dynamically regulates protein functions and gene expression by covalently attaching lactate groups to lysine residues. Recent studies have shown that abnormal lactate metabolism not only contributes to the pathogenesis of epilepsy through microenvironment acidification but also influences neuroinflammation, energy metabolism imbalance, neurotransmitter dysregulation, synaptic plasticity, and epigenetic regulation via lactylation. This positions lactylation as a critical metabolic-epigenetic intersection in the pathological mechanisms of epilepsy.
View Article and Find Full Text PDFNeurobiol Dis
September 2025
Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX, USA; Brain Health Consortium, The University of Texas at San Antonio, San Antonio, TX, USA. Electronic address:
Temporal lobe epilepsy is associated with aberrant neurogenesis and ectopic migration of adult-born granule cells (abGCs), yet the molecular mechanisms driving these changes remain poorly defined. Using a pilocarpine-induced mouse model of temporal lobe epilepsy and chemogenetic silencing of abGCs via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we previously demonstrated that abGC inhibition reduces both ectopic migration and seizure susceptibility. To identify underlying molecular regulators, we performed RNA sequencing of FACS-isolated abGCs and identified Rrm2 and Timp3 as top candidate genes modulated by seizure activity and neuronal silencing.
View Article and Find Full Text PDFBrain Res Bull
September 2025
Department of Neuroscience of Disease, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan. Electronic address:
Mutations in the UBE3A gene are responsible for neurodevelopmental disorders (NDDs), including Angelman syndrome (AS), which is characterized by developmental delays, impaired motor coordination, and cognitive disabilities. In recent years, UBE3A mutations have also been linked to autism spectrum disorders (ASD), due to their significant role in synaptic plasticity and cognitive function. Although substantial research has utilized mammalian models, the zebrafish (Danio rerio) provides unique opportunities to investigate gene functions owing to their transparent embryos, rapid development, and suitability for large-scale genetic and behavioral studies.
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