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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Dysregulation of brain adenosine is detrimental to the expression of conditioned freezing but not general Pavlovian learning.
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Dysregulation of brain adenosine is detrimental to the expression of conditioned freezing but not general Pavlovian learning.

机译：脑腺苷的失调对条件冻结但不是普通帕夫洛维亚学习的表达有害。

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摘要

Glutamatergic and dopaminergic neurotransmission is modulated by adenosine, whose ambient level in the brain is in turn regulated by the metabolic enzyme, adenosine kinase (ADK). Brain adenosinergic tone can therefore be effectively reduced and increased by up- and down-regulation of ADK expression, respectively. Although changes in brain ADK levels can yield multiple behavioral effects, the precise functional significance of telencephalon (neocortical and limbic structures) adenosine remains ill-defined. Among the phenotypes identified in transgenic mice with brain-wide ADK overexpression (ADK(TG) mice) and reduced adenosinergic tone, working memory deficiency and potentiated response to systemic N-methyl-d-aspartate receptor blockade were exacerbated by the introduction of local ADK disruption (elevated adenosinergic tone) restricted to the telencephalon (ADK(TG):ADK(Tel-def) mice). These two phenotypes, which are central to schizophrenia cognitive/negative symptoms, appear to be regulated by adenosinergic activities within and outside the telencephalon in a complementary manner. Here, we extended this unique comparison between ADK(TG) mice ADK(TG):ADK(Tel-def) mice to another prominent phenotype previously documented in ADK(TG) mice - namely, impaired Pavlovian conditioned freezing. We found that ADK(TG):ADK(Tel-def) mice again were associated with a more severe phenotype while sharing a similar phenotype profile. Furthermore, we qualified that this Pavlovian phenotype did not translate into a general deficiency in associative learning, since no such deficit was evident in three other (aversive and appetitive) Pavlovian learning paradigms. The present study has thus identified a hitherto unknown function of brain adenosine: the execution of conditioned freezing behavior, which is dependent on the balance of adenosinergic changes between the telencephalon and the rest of the brain.
机译：氨基氨基调节谷氨酸和多巴胺能神经递质，腺苷的调节，其脑中的环境水平反过来由代谢酶，腺苷激酶（ADK）调节。因此，通过分别可以有效地减少和降低ADK表达的下调和下调脑腺苷能色调。虽然脑ADK水平的变化可以产生多种行为效应，但斜视（Neocortical和肢体结构）腺苷的精确功能意义仍然是不明定义的。在具有脑宽ADK过表达（ADK（Tg）小鼠的转基因小鼠中鉴定的表型，并通过引入局部ADK加剧了对全身N-甲基-D-天冬氨酸受体阻滞的工作记忆缺陷和增强的反应。受破坏（腺嘌呤能学音）限于斜视（ADK（TG）：ADK（TEL-DEF）小鼠）。这两种表型是精神分裂症认知/阴性症状的核型，似乎受到互补的方式的腺嘌呤能活性和外部外部的腺嘌呤能活性。在这里，我们将ADK（TG）小鼠ADK（TG）：ADK（TEL-DEF）小鼠之间的这种独特的比较扩展到以前在ADK（TG）小鼠中的另一个突出表型 - 即Pavlovian调节冻结受损。我们发现ADK（TG）：ADK（TEL-DEF）小鼠再次与更严重的表型相关联，同时共用类似的表型简档。此外，我们有资格获得这种帕夫洛夫表型并未转化为联想学习的一般缺陷，因为在另外三个（厌恶和快乐）Pavlovian学习范式中没有明显的赤字。因此，本研究鉴定了脑腺苷的迄今为止未知功能：调节冻结行为的执行，这取决于视线与大脑其余的腺苷能变化的平衡。

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