γ-氨基丁酸B（1）受体亚型在认知中的特定作用。
Specific roles of GABA(B(1)) receptor isoforms in cognition.
作者信息
Jacobson Laura H, Kelly Peter H, Bettler Bernhard, Kaupmann Klemens, Cryan John F
机构信息
Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland.
出版信息
Behav Brain Res. 2007 Jul 19;181(1):158-62. doi: 10.1016/j.bbr.2007.03.033. Epub 2007 Apr 5.
The GABA(B) receptor is a heterodimer of GABA(B(1)) and GABA(B(2)) subunits. There are two isoforms of the GABA(B(1)) subunit: GABA(B(1a)) and GABA(B(1b)). Recent studies with mutant mice suggest a differential role for the two GABA(B(1)) isoforms in behavioural processes. As pharmacological and genetic studies have implicated GABA(B) receptors in cognition we investigated the behaviour of GABA(B(1a))(-/-) and GABA(B(1b))(-/-) mice in different types of cognitive paradigms. GABA(B(1a))(-/-) and GABA(B(1b))(-/-) mice were both impaired relative to wildtype controls in a continuous spontaneous alternation behaviour test of working spatial memory. In contrast to the reported phenotype of GABA(B(1))(-/-) mice, however, neither GABA(B(1a))(-/-) nor GABA(B(1b))(-/-) mice were deficient in a passive avoidance task. On the other hand, GABA(B(1a))(-/-) mice were impaired in familiar and novel object recognition. We conclude that GABA(B(1)) isoforms contribute differentially to GABA(B) receptor-mediated cognitive processes.
GABA(B)受体是GABA(B(1))和GABA(B(2))亚基的异源二聚体。GABA(B(1))亚基有两种异构体：GABA(B(1a))和GABA(B(1b))。最近对突变小鼠的研究表明，这两种GABA(B(1))异构体在行为过程中具有不同的作用。由于药理学和遗传学研究表明GABA(B)受体与认知有关，我们研究了GABA(B(1a))基因敲除和GABA(B(1b))基因敲除小鼠在不同类型认知范式中的行为。在工作空间记忆的连续自发交替行为测试中，GABA(B(1a))基因敲除和GABA(B(1b))基因敲除小鼠相对于野生型对照均表现受损。然而，与报道的GABA(B(1))基因敲除小鼠的表型不同，GABA(B(1a))基因敲除和GABA(B(1b))基因敲除小鼠在被动回避任务中均未表现出缺陷。另一方面，GABA(B(1a))基因敲除小鼠在熟悉和新物体识别方面表现受损。我们得出结论，GABA(B(1))异构体对GABA(B)受体介导的认知过程有不同的贡献。
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