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

Mishima, Tatsuya; Fujiwara, Tomonori; Kofuji, Takefumi; Akagawa, Kimio

doi:10.1523/jneurosci.2911-11.2012

Cited by 29 publications

(25 citation statements)

References 59 publications

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“…Using immunohistochemical labeling, we also showed a concordant increase in STX1A protein expression within the hippocampus of cKO animals. STX1A plays a central role in the docking of presynaptic vesicles via the formation of the SNARE complex and is required for normal hippocampal LTP (Bennett et al 1992;Mishima et al 2012). While STX1A is essential for voltagedependent calcium and potassium signaling (and thus for synaptic transmission), its overexpression inhibits exocytosis and blocking STX1A enhances Ca 2+ influx into cells via N-type calcium channels (Mitchell and Ryan 2005;Swayne et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

et al. 2016

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miR-132 and miR-212 are structurally related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same noncoding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/-212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/-212 double-knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/-212 double-knockout line to explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/-212 deletion increased the expression of 1138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/-212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that these two genes may function in a complex, nonredundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/-212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders.

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Section: Discussionmentioning

confidence: 99%

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

et al. 2016

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“…Previously, we reported that deletion of STX1A has no effect on evoked or spontaneous fast synaptic transmission, although impairments are seen in hippocampal monoaminergic transmission, long-term potentiation and learning ability [12], [13]. This phenotype might be due to compensation by STX1B, because these isoforms are highly homologous.…”

Section: Introductionmentioning

confidence: 89%

Syntaxin 1B, but Not Syntaxin 1A, Is Necessary for the Regulation of Synaptic Vesicle Exocytosis and of the Readily Releasable Pool at Central Synapses

et al. 2014

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Two syntaxin 1 (STX1) isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t)-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission.

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“…S2). However, unlike Stx1a −/− or Stx1a +/− (Mishima et al ., ), the elevation in monoamine concentrations following high K stimulation was not different between WT and Stx1b +/− mice. Interestingly, the DA concentration in the basal condition was higher in Stx1b +/− compared with WT mice, although the 5‐HT and NE concentrations in the basal condition were not different (Fig.…”

Section: Resultsmentioning

confidence: 99%

Syntaxin 1B contributes to regulation of the dopaminergic system through GABA transmission in the CNS

Fujiwara

Kofuji

Mishima

et al. 2017

Eur J of Neuroscience

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In neuronal plasma membrane, two syntaxin isoforms, HPC-1/syntaxin 1A (STX1A) and syntaxin 1B (STX1B), are predominantly expressed as soluble N-ethylmaleimide-sensitive fusion attachment protein receptors, also known as t-SNAREs. We previously reported that glutamatergic and GABAergic synaptic transmissions are impaired in Stx1b null mutant (Stx1b ) mice but are almost normal in Stx1a null mutant (Stx1a ) mice. These observations suggested that STX1A and STX1B have distinct functions in fast synaptic transmission in the central nervous system (CNS). Interestingly, recent studies indicated that Stx1a or Stx1a mice exhibit disruption in the monoaminergic system in the CNS, causing unusual behaviour that is similar to neuropsychological alterations observed in psychiatric patients. Here, we studied whether STX1B contributes to the regulation of monoaminergic system and if STX1B is related to neuropsychological properties in human neuropsychological disorders similar to STX1A. We found that monoamine release in vitro was normal in Stx1b mice unlike Stx1a or Stx1a mice, but the basal extracellular dopamine (DA) concentration in the ventral striatum was increased. DA secretion in the ventral striatum is regulated by GABAergic neurons, and Stx1b mice exhibited reduced GABA release both in vitro and in vivo, disrupting the DAergic system in the CNS of these mice. We also found that Stx1b mice exhibited reduced pre-pulse inhibition (PPI), which is believed to represent one of the prominent schizotypal behavioural profiles of human psychiatric patients. The reduction in PPI was rescued by DA receptor antagonists. These observations indicated that STX1B contributes to excess activity of the DAergic system through regulation of GABAergic transmission.

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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

Cited by 29 publications

References 59 publications

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

Syntaxin 1B, but Not Syntaxin 1A, Is Necessary for the Regulation of Synaptic Vesicle Exocytosis and of the Readily Releasable Pool at Central Synapses

Syntaxin 1B contributes to regulation of the dopaminergic system through GABA transmission in the CNS

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