Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 46, Issue 12, Pages 2867-2874Publisher
WILEY
DOI: 10.1111/ejn.13779
Keywords
invivo microdialysis; knockout mice; monoamine; pre-pulse inhibition; syntaxin 1B
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan [16K01954, 24300142]
- Promotion and Mutual Aid Cooperation for Private Schools of Japan
- Grants-in-Aid for Scientific Research [16K01954] Funding Source: KAKEN
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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 invitro 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 invitro and invivo, 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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