Small-Conductance Ca2+-Activated Potassium Type 2 Channels Regulate the Formation of Contextual Fear Memory
Open accessAbstract
Small-conductance, Ca2+ activated K+ channels (SK channels) are expressed at high levels in brain regions responsible for learning and memory. In the current study we characterized the contribution of SK2 channels to synaptic plasticity and to different phases of hippocampal memory formation. Selective SK2 antisense-treatment facilitated basal synaptic transmission and theta-burst induced LTP in hippocampal brain slices. Using the selective SK2 antagonist Lei-Dab7 or SK2 antisense probes, we found that hippocampal SK2 channels are critical during two different time windows: 1) blockade of SK2 channels before the training impaired fear memory, whereas, 2) blockade of SK2 channels immediately after the training enhanced contextual fear memory. We provided the evidence that the post-training cleavage of the SK2 channels was responsible for the observed bidirectional effect of SK2 channel blockade on memory consolidation. Thus, Lei-Dab7-injection before training impaired the C-terminal cleavage of SK2 channels, while Lei-Dab7 given immediately after training facilitated the C-terminal cleavage. Application of the synthetic peptide comprising a leucine-zipper domain of the C-terminal fragment to Jurkat cells impaired SK2 channel-mediated currents, indicating that the endogenously cleaved fragment might exert its effects on memory formation by blocking SK2 channel-mediated currents. Our present findings suggest that SK2 channel proteins contribute to synaptic plasticity and memory not only as ion channels but also by additionally generating a SK2 C-terminal fragment, involved in both processes. The modulation of fear memory by down-regulating SK2 C-terminal cleavage might have applicability in the treatment of anxiety disorders in which fear conditioning is enhanced.
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The observed excess in ASD subjects of alleles positively associated with educational attainment is confined to Asperger's and childhood autism, and is not seen in atypical autism nor other/unspecified PDD.
“We find that the observed excess in ASD subjects of alleles positively associated with education attainment 85,86 is confined to Asperger's and childhood autism, and it is not seen here in atypical autism nor in other/unspecified PDD.”
From Identification of common genetic risk variants for autism spectrum disorder (2019) · cites this paper as [86]
The cited paper’s Introduction and Results address SK2 channels, synaptic plasticity, and fear memory in mice, not educational-attainment-associated alleles in ASD subjects. Searches for the ASD subtypes and educational-attainment alleles found no passage addressing the cited background claim. The subtype restriction is presented as the citing authors’ own finding, rather than a finding attributed to this source. (LLM, conf=0.77)
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- Authors
- Murthy, S. R. K., Sherrin, T., Jansen, C., Nijholt, I., Robles, M., Dolga, A. M., Andreotti, N., Sabatier, J.-M., Knaus, H.-G., Penner, R., Todorovic, C., & Blank, T.
- Affiliations
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- University of Hawaiʻi at Mānoa (US)
- Isala (NL)
- Philipps University of Marburg (DE)
- Inserm (FR)
- Innsbruck Medical University (AT)
- Corresponding author
- Todorovic, Cedomir
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-05-04
- Volume
- 10
- Issue
- 5
- Pages
- e0127264
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4418695
- OpenAlex
- W258404711
- Cited by
- 16
- References
- 34
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 1
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R21MH086733, MH086733)
- National Institute on Minority Health and Health Disparities (U54MD008149, G12MD007601)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- small conductance calcium-activated potassium channels, SK2 channel, contextual fear memory, memory consolidation, hippocampus, synaptic plasticity, long-term potentiation, leucine zipper domain, fear conditioning, anxiety disorders
- MeSH terms
- Animals, Fear, Hippocampus, Male, Memory, Mice, Inbred C57BL, Long-Term Potentiation, Mice, Small-Conductance Calcium-Activated Potassium Channels
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