GABA-A and GABA-B Receptors in Filial Imprinting Linked With Opening and Closing of the Sensitive Period in Domestic Chicks (Gallus gallus domesticus)
GABA-A and GABA-B Receptors in Filial Imprinting Linked With Opening and Closing of the Sensitive Period in Domestic Chicks (Gallus gallus domesticus)
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DOI：
10.3389/fphys.2018.01837
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发表时间：
2018-12-19
影响因子：
4
通讯作者：
Homma, Koichi J.
中科院分区：
文献类型：
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作者：
Aoki, Naoya;Yamaguchi, Shinji;Homma, Koichi J.
家鸡的子代印记有一个明确的敏感(关键)时期，在实验室中从孵化到3日龄。这是研究早期学习记忆形成的分子机制的典型模型。我们最近发现，甲状腺激素3，5，3‘-三碘甲腺原氨酸(T-3)是敏感期的决定因素。大脑T-3水平的快速增加是由印记训练引起的，使小鸡变得可印记。此外，即使在敏感期结束后，注射外源性T-3也能使雏鸡在第4天或第6天印上印记。然而，T-3如何影响神经传递从而使印记成为可能仍是个未知数。在这项研究中，我们证明了在T-3下游印迹中，伽马-氨基丁酸(GABA)-A和GABA-B受体的相反作用。定量逆转录聚合酶链式反应和免疫印迹结果显示，GABA-A受体的表达从第1天到第5天逐渐增加，而GABA-B受体的表达逐渐减少。我们检查了负责印记的大脑区域中间中间系膜(IMM)的神经元是否表达这两种类型的GABA受体。免疫组织化学染色显示，形态上已确定的投射神经元同时表达GABA-A和GABA-B受体，提示这些GABA受体在这些细胞中相互作用以调节IMM的输出。用不同的激动剂和拮抗剂研究GABA-A和GABA-B受体的作用。我们的结果表明，GABA-B受体拮抗剂在第1天抑制印记，而它的激动剂使第4天的雏鸡可以印记。不注射外源性T-3。相反，GABA-A受体激动剂在第1天抑制印记，而其拮抗剂在没有外源T-3的情况下在第4天诱导印记。此外，在敏感期结束后的第4天，GABA-A受体激动剂和GABA-B受体拮抗剂都抑制T-3诱导的印迹。我们的药理实验数据表明，GABA-B受体通过启动敏感期来促进T-3下游的印迹，而GABA-A受体有助于敏感期的终止。总之，我们认为GABA-A和GABA-B受体在大脑发育过程中的相反作用决定了敏感期的诱导和终止。
Filial imprinting of domestic chicks has a well-defined sensitive (critical) period lasting in the laboratory from hatching to day 3. It is a typical model to investigate the molecular mechanisms underlying memory formation in early learning. We recently found that thyroid hormone 3,5,3'-triiodothyronine (T-3 ) is a determinant of the sensitive period. Rapid increases in cerebral T-3 levels are induced by imprinting training, rendering chicks imprintable. Furthermore, the administration of exogenous T-3 makes chicks imprintable on days 4 or 6 even after the sensitive period has ended. However, how T-3 affects neural transmission to enable imprinting remains mostly unknown. In this study, we demonstrate opposing roles for gamma-aminobutyric acid (GABA)-A and GABA-B receptors in imprinting downstream of T-3. Quantitative reverse transcription polymerase chain reaction and immunoblotting showed that the GABA-A receptor expression increases gradually from days 1 to 5, whereas the GABA-B receptor expression gradually decreases. We examined whether neurons in the intermediate medial mesopallium (IMM), the brain region responsible for imprinting, express both types of GABA receptors. Immunostaining showed that morphologically identified putative projection neurons express both GABA-A and GABA-B receptors, suggesting that those GABA receptors interact with each other in these cells to modulate the IMM outputs. The roles of GABA-A and GABA-B receptors were investigated using various agonists and antagonists. Our results show that GABA-B receptor antagonists suppressed imprinting on day 1, while its agonists made day 4 chicks imprintable. without administration of exogenous T-3. By contrast, GABA-A receptor agonists suppressed imprinting on day 1, while its antagonists induced imprintability on day 4 without exogenous T-3. Furthermore, both GABA-A receptor agonists and GABA-B receptor antagonists suppressed T-3-induced imprintability on day 4 after the sensitive period has ended. Our data from these pharmacological experiments indicate that GABA-B receptors facilitate imprinting downstream of T-3 by initiating the sensitive period, while the GABA-A receptor contributes to the termination of the sensitive period. In conclusion, we propose that opposing roles of GABA-A and GABA-B receptors in the brain during development determine the induction and termination of the sensitive period.