ArticlePloS one2011
Dynamic changes in neurexins' alternative splicing: role of Rho-associated protein kinases and relevance to memory formation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Roles of NRXN1 in neuropsychiatric disorders: from genetic lesion to molecular mechanism.Frontiers in neuroscience · 2026Review
- Targeting ROCK2 to Restore Epileptic Synaptic Networks via Mitophagy Activation: Insights from Translational Imaging of SV2A In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Modulation of Neurexins Alternative Splicing by Cannabinoid Receptors 1 (CB1) Signaling.Cells · 2025Article
- Transcriptionally downregulated GABAergic genes associated with synaptic density network dysfunction in temporal lobe epilepsy.European journal of nuclear medicine and molecular imaging · 2025Article
- New insights on the regulators and inhibitors of RhoA-ROCK signalling in Parkinson's disease.Metabolic brain disease · 2025Review
- Gnao1 is a molecular switch that regulates the Rho signaling pathway in differentiating neurons.Scientific reports · 2024Article
- Neurexins and their ligands at inhibitory synapses.Frontiers in synaptic neuroscience · 2022Review
- Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex.Journal of functional morphology and kinesiology · 2021Article
- Mild Amnestic Cognitive Impairment and Depressive Symptoms in Autoimmune Encephalitis Associated with Serum Anti-Neurexin-3α Autoantibodies.Brain sciences · 2021Article
- The Perils of Navigating Activity-Dependent Alternative Splicing of Neurexins.Frontiers in molecular neuroscience · 2021Article
- Neuronal impact of patient-specific aberrant NRXN1α splicing.Nature genetics · 2019Article
- Genetic insights and neurobiological implications from NRXN1 in neuropsychiatric disorders.Molecular psychiatry · 2019Review
- Comparative Study of ROCK1 and ROCK2 in Hippocampal Spine Formation and Synaptic Function.Neuroscience bulletin · 2019Article
- Review
- Contextual fear conditioning induces differential alternative splicing.Neurobiology of learning and memory · 2016Article
- Neurexin 1 (NRXN1) splice isoform expression during human neocortical development and aging.Molecular psychiatry · 2016Article
- Article
- Dystroglycan binding to α-neurexin competes with neurexophilin-1 and neuroligin in the brain.The Journal of biological chemistry · 2014Article
- Emerging mechanisms and consequences of calcium regulation of alternative splicing in neurons and endocrine cells.Cellular and molecular life sciences : CMLS · 2013Review
- Exonal elements and factors involved in the depolarization-induced alternative splicing of neurexin 2.Journal of molecular neuroscience : MN · 2013Article
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4 authors.
Funding
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Abstract
The three neurexins genes (NRXN1/2/3) encode polymorphic synaptic membrane proteins that are involved in cognitive functioning. Neurexins' selectivity of function is presumably conferred through differential use of 2 promoters and 5 alternative splicing sites (SS#1/2/3/4/5). In day-old rat brain neurons grown in culture, activation (depolarization) induces reversible, calcium dependent, repression of NRXN2α SS#3 insert. The effects of depolarization on NRXN1/2/3α splicing and biochemical pathways mediating them were further studied in these neurons. NRXN1/2/3α splicing in the course of memory formation in vivo was also explored, using fear conditioning paradigm in rats in which the animals were trained to associate an aversive stimulus (electrical shock) with a neutral context (a tone), resulting in the expression of fear responses to the neutral context.In the cultured neurons depolarization induced, beside NRXN2α SS#3, repression of SS#3 and SS#4 exons in NRXN3α but not NRXN1α. The repressions were mediated by the calcium/protein kinase C/Rho-associated protein kinase (ROCK) pathway. Fear conditioning induced significant and transient repressions of the NRXN1/2/3α SS#4 exons in the rat hippocampus. ROCK inhibition prior to training attenuated the behavioral fear response, the NRXN1/2/3α splicing repressions and subsequent recovery and the levels of excitatory (PSD95) and inhibitory (gephyrin) synaptic proteins in the hippocampus. No such effects were observed in the prefrontal cortex. Significant correlations existed between the fear response and hippocampal NRXN3α and NRXN2α SS#4 inserts as well as PSD95 protein levels. Hippocampal NRXN1α SS#4 insert and gephyrin levels did not correlate with the behavioral response but were negatively correlated with each other.These results show for the first time dynamic, experience related changes in NRXN1/2/3α alternative splicing in the rat brain and a role for ROCK in them. Specific neurexins' transcripts may be involved in synaptic remodeling occurring at an intermediate (hours) time scale in the course of memory formation.
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