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Analysis of Knock-Out Mice to Determine the Role of HPC-1/Syntaxin 1A in Expressing Synaptic Plasticity
Open accessAbstract
The protein HPC-1/syntaxin 1A is abundantly expressed in neurons and localized in the neuronal plasma membrane. It forms a complex with SNAP-25 (25 kDa synaptosomal-associated protein) and VAMP-2 (vesicle-associated membrane protein)/synaptobrevin called SNARE (a soluble N -ethylmaleimide-sensitive fusion protein attachment protein receptor) complex, which is considered essential for synaptic vesicle exocytosis; thus, HPC-1/syntaxin 1A is considered crucial for synaptic transmission. To examine the physiological function of HPC-1/syntaxin 1A in vivo , we produced knock-out (KO) mice by targeted gene disruption. Although HPC-1/syntaxin 1A expression was completely depleted without any effect on the expression of other SNARE proteins, the KO mice were viable. They grew normally, were fertile, and displayed no difference in appearance compared with control littermate. In cultured hippocampal neurons derived from the KO mice, the basic synaptic transmission in vitro was normal. However, the mutant mice had impaired long-term potentiation in the hippocampal slice. Also, although KO mice exhibited normal spatial memory in the hidden platform test, consolidation of conditioned fear memory was impaired. Interestingly, the KO mice had impaired conditioned fear memory extinction. These observations suggest that HPC-1/syntaxin 1A may be closely related to synaptic plasticity.
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“have already identified CAPGLY domain containing linker protein 2 (CLIP2), LIM domain kinase 1 (LIMK1), General transcription factor II, i (GTF2i), and Syntaxin 1A (STX1A) as the leading candidates among the 22 genes within the region for involvement in the cognitive and social phenotypes.”
From Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism (2011) · cites this paper as Fujiwara et al., 2006
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Metadata
- Authors
- Fujiwara, T., Mishima, T., Kofuji, T., Chiba, T., Tanaka, K., Yamamoto, A., & Akagawa, K.
- Affiliations
- Kyorin University (JP)
- University of Tsukuba (JP)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Nagahama Institute of Bio-Science and Technology (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-05-24
- Volume
- 26
- Issue
- 21
- Pages
- 5767-5776
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6675267
- OpenAlex
- W2036209745
- Cited by
- 125
- References
- 58
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 9 · 2013: 5 · 2012: 8
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- syntaxin 1A, synaptic plasticity, long-term potentiation, SNARE complex, synaptic vesicle exocytosis, synaptic transmission, conditioned fear memory, fear extinction, spatial memory, hippocampal neurons, knockout mice
- MeSH terms
- Animals, Hippocampus, Synaptic Transmission, Neuronal Plasticity, Neurons, Synapses, Long-Term Potentiation, Syntaxin 1, Mice
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