Analysis of Knock-Out Mice to Determine the Role of HPC-1/Syntaxin 1A in Expressing Synaptic Plasticity

Fujiwara, Tomonori; Mishima, Tatsuya; Kofuji, Takefumi; Chiba, Tomoki; Tanaka, Keiji; Yamamoto, Akira; Akagawa, Kimio

doi:10.1523/jneurosci.0289-06.2006

Cited by 119 publications

(159 citation statements)

References 59 publications

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“…The mice were kept under a 12 h light/dark cycle (lights on at 6:00 A.M.), and food and water were available ad libitum. STX1A Ϫ/Ϫ mice were generated as previously described (Fujiwara et al, 2006). Most of the experiments were performed using littermate WT and STX1A…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, late LTP requires the activation of adenylyl cyclase and PKA (Nguyen and Kandel, 1997;Otmakhova et al, 2000). We previously reported that HPC-1/syntaxin 1A knock-out (STX1A Ϫ/Ϫ ) mice had impaired LTP in the CA1 area of the hippocampus based on an analysis of brain slices (Fujiwara et al, 2006). Also, consolidation of contextual fear memory was im-paired.…”

Section: Introductionmentioning

confidence: 99%

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Impairment of Catecholamine Systems during Induction of Long-Term Potentiation at Hippocampal CA1 Synapses in HPC-1/Syntaxin 1A Knock-out Mice

Mishima

Fujiwara²,

Kofuji³

et al. 2012

J. Neurosci.

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The membrane protein HPC-1/syntaxin 1A is believed to play a key role in synaptic vesicle exocytosis, and it was recently suggested to be required for synaptic plasticity. Despite evidence for the function of HPC-1/syntaxin 1A in synaptic plasticity, the underlying cellular mechanism is unclear. We found that although fast synaptic transmission and long-term depression were unaffected, HPC-1/syntaxin 1A knock-out (STX1A Ϫ/Ϫ ) mice showed impaired long-term potentiation (LTP) in response to theta-burst stimulation in CA1 hippocampal slices. The impairment in LTP was rescued by the application of forskolin, an adenylyl cyclase activator, or more robust stimulation, suggesting that cAMP/protein kinase A signaling was suppressed in these mice. In addition, catecholamine release from the hippocampus was significantly reduced in STX1A Ϫ/Ϫ mice. Because HPC-1/syntaxin 1A regulates exocytosis of dense-core synaptic vesicles, which contain neuromodulatory transmitters such as noradrenaline, dopamine and 5-HT, we examined the effect of neuromodulatory transmitters on LTP induction. Noradrenaline and dopamine enhanced LTP induction in STX1A Ϫ/Ϫ mice, whereas catecholamine depletion reduced LTP induction in wild-type mice. Theses results suggest that HPC-1/syntaxin 1A regulates catecholaminergic systems via exocytosis of dense-core synaptic vesicles, and that deletion of HPC-1/syntaxin 1A causes impairment of LTP induction.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impairment of Catecholamine Systems during Induction of Long-Term Potentiation at Hippocampal CA1 Synapses in HPC-1/Syntaxin 1A Knock-out Mice

Mishima

Fujiwara²,

Kofuji³

et al. 2012

J. Neurosci.

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“…The genetic alteration of STX1A levels might also contribute to impaired glucose metabolism, which occurs with increased incidence in adults with WBS [23,163,164]. In cognitive functional test, Stx1a knock out mice demonstrated an increased conditioned fear memory lacking any other difference in appearance compared with control littermate [165].…”

Section: The Single Copy Gene Part Of the Wbs Regionmentioning

confidence: 99%

The genomic basis of the Williams – Beuren syndrome

Schubert

2008

Cell. Mol. Life Sci.

214

161

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. The Williams-Beuren syndrome is a genomic disorder (prevalence: 1/7,500 to 1/20,000), caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Typical symptoms comprise supravalvular aortic stenosis, mental retardation, overfriendliness and visuospatial impairment. The common deletion sizes range of 1.5–1.8 mega base pairs (Mb), encompassing app. 28 genes. For a few genes, a genotype-phenotype correlation has been established. The best-explored gene within this region is the elastin gene; its haploinsufficiency causes arterial stenosis. The region of the Williams-Beuren syndrome consists of a single copy gene region (~1.2 Mb) flanked by repetitive sequences – Low Copy Repeats (LCR). The deletions arise as a consequence of misalignment of these repetitive sequences during meiosis and a following unequal crossing over due to high similarity of LCRs. This review presents an overview of the Williams-Beuren syndrome region considering the genomic assembly, chromosomal rearrangements and their mechanisms (i.e. deletions, duplications, inversions) and evolutionary and historical aspects.

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“…No learning and memory deficits 53,54 Impaired long-term potentiation and memory consolidation 53 N/A High embryonic lethality 54…”

Section: Baz1bmentioning

confidence: 99%

“…Single-gene knockout mouse models were also generated. [15][16][17][18] While most of heterozygous mice for each gene exhibited some relevant phenotypes, one of them (Fkbp6) showed no phenotype at all unless both alleles were knocked out, 19 suggesting that symptomatic traits could be the result of either interaction between more than one gene or the physiologic differences between mouse and human. Recently, a mouse model for WS with full hemizygous deletion has been successfully created and recapitulated most of phenotypes in human including total brain volume reduction, increased social interaction, hypersensitivity to sound and mild motor deficits.…”

mentioning

confidence: 99%