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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性冰冻的表达有害，但对一般的巴甫洛夫式学习不利。

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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 cognitiveegative 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：谷氨酸能和多巴胺能神经传递是由腺苷调节的，腺苷在大脑中的环境水平又由代谢酶腺苷激酶（ADK）调节。因此，分别通过上调和下调ADK表达可以有效地减少和增加脑腺苷能的语调。尽管大脑ADK水平的改变会产生多种行为影响，但端脑腺（神经和边缘结构）腺苷的确切功能意义仍不清楚。在具有全脑ADK过表达的转基因小鼠（ADK（TG）小鼠）和降低的腺苷能张力的转基因小鼠中鉴定出的表型中，通过引入局部ADK加剧了工作记忆缺陷和对系统性N-甲基-d-天冬氨酸受体阻滞的增强反应破坏（腺苷能音调升高）仅限于端脑（ADK（TG）：ADK（Tel-def）小鼠）。这两个表型是精神分裂症认知/阴性症状的核心，似乎由端脑内部和外部的腺苷能活动以互补的方式调节。在这里，我们将ADK（TG）小鼠ADK（TG）：ADK（Tel-def）小鼠之间的这种独特比较扩展到了以前在ADK（TG）小鼠中记录的另一个突出表型-即受损的巴甫洛夫条件冷冻。我们发现，ADK（TG）：ADK（Tel-def）小鼠再次与更严重的表型相关，同时具有相似的表型特征。此外，我们证明了这种巴甫洛夫表型不会转化为联想学习中的普遍缺陷，因为在其他三种（渐进式和富有吸引力的）巴甫洛夫学习范式中均未发现这种缺陷。因此，本研究已经确定了脑腺苷的迄今未知的功能：条件性冰冻行为的执行，这取决于端脑与大脑其余部分之间腺苷能变化的平衡。

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