ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 188 citations in OpenAlex.
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- A Sleeping Opportunity Does Not Restore Hippocampal Alterations Induced by 10 Days of Sleep Restriction in Rats.Neurochemical research · 2025Article
- A specific negatively charged sequence confers intramolecular regulation on Munc13-1 function in synaptic exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models.The Journal of clinical investigation · 2025Article
- Inhibition of hippocampal mossy fiber plasticity and episodic memory by human Aβ oligomers is prevented by enhancing cAMP signaling in Alzheimer's mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Rasopathy-Associated Mutation Ptpn11Cellular and molecular neurobiology · 2024Article
- PTPN11/Corkscrew Activates Local Presynaptic Mapk Signaling to Regulate Synapsin, Synaptic Vesicle Pools, and Neurotransmission Strength, with a Dual Requirement in Neurons and Glia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Neuronal Protection by Ha-RAS-GTPase Signaling through Selective Downregulation of Plasmalemmal Voltage-Dependent Anion Channel-1.International journal of molecular sciences · 2024Article
- Hydroxynorketamine, but not ketamine, acts via α7 nicotinic acetylcholine receptor to control presynaptic function and gene expression.Translational psychiatry · 2024Article
- Deletion of Small GTPase H-Ras Rescues Memory Deficits and Reduces Amyloid Plaque-Associated Dendritic Spine Loss in Transgenic Alzheimer's Mice.Molecular neurobiology · 2023Article
- FMRP activity and control of Csw/SHP2 translation regulate MAPK-dependent synaptic transmission.PLoS biology · 2023Article
- Review
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- Corticostriatal dysfunction and social interaction deficits in mice lacking the cystine/glutamate antiporter.Molecular psychiatry · 2021Article
- Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus.Scientific reports · 2021Article
- Alcohol Enhances Responses to High Frequency Stimulation in Hippocampus from Transgenic Mice with Increased Astrocyte Expression of IL-6.Cellular and molecular neurobiology · 2021Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Molecular and cellular studies of the mechanisms underlying mammalian learning and memory have focused almost exclusively on postsynaptic function. We now reveal an experience-dependent presynaptic mechanism that modulates learning and synaptic plasticity in mice. Consistent with a presynaptic function for endogenous H-ras/extracellular signal-regulated kinase (ERK) signaling, we observed that, under normal physiologic conditions in wild-type mice, hippocampus-dependent learning stimulated the ERK-dependent phosphorylation of synapsin I, and MEK (MAP kinase kinase)/ERK inhibition selectively decreased the frequency of miniature EPSCs. By generating transgenic mice expressing a constitutively active form of H-ras (H-rasG12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesicles in glutamatergic terminals, an increased frequency of miniature EPSCs, and increased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.