Circadian pacemaker neurons of the Madeira cockroach are inhibited and activated by GABAA and GABAB receptors
Circadian pacemaker neurons of the Madeira cockroach are inhibited and activated by GABAA and GABAB receptors
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DOI：
10.1111/ejn.14268
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发表时间：
2018-12
影响因子：
3.4
通讯作者：
M. Giese;Hongying Wei;M. Stengl
中科院分区：
文献类型：
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作者：
M. Giese;Hongying Wei;M. Stengl
GABA是哺乳动物和昆虫昼夜节律起搏器回路中最丰富的神经递质。马德拉蟑螂大脑视叶中的副髓质（AME）是生物钟，它与光暗周期同步协调休息-活动节奏。三个突出的gaba能束将AME连接到复眼光感受器在板和髓质的终止位点。平行伽马氨基丁酸能光携带路径被认为可以提前或延迟时钟以适应不断变化的光周期。与这一假设一致，GABA激活或抑制AME时钟神经元，允许区分三种不同的GABA反应类型。在这里，我们研究了哪些GABA受体负责这些反应类型。我们发现，嗜离子性GABAA受体和代谢性GABAB受体在AME时钟细胞中均有表达。通过不同的信号传导途径，它们中的任何一种都可以解释所有三种GABA反应类型。muscimol依赖性激活的GABAA受体形成了一个氯离子通道，而SKF 97541依赖性激活的GABAB受体通过G蛋白信号传导，明显靶向钾离子通道。氯化物输出或输入的表达决定GABAA受体是否激活超极化或去极化AME神经元。对于GABA受体反应，时钟细胞中存在的第二信使门控通道似乎决定了GABA反应的极性。综上所述，生物钟神经元以不同的组合共同表达抑制性和/或兴奋性GABAA和GABAB受体，而共转运蛋白的表达和第二信使门控离子通道的存在允许不同生物钟神经元中不同的信号传导。
GABA is the most abundant neurotransmitter in the circadian pacemaker circuits of mammals and insects. In the Madeira cockroach the accessory medulla (AME) in the brain′s optic lobes is the circadian clock that orchestrates rest‐activity rhythms in synchrony with light dark cycles. Three prominent GABAergic tracts connect the AME to termination sites of compound eye photoreceptors in the lamina and medulla. Parallel GABAergic light entrainment pathways were suggested to either advance or delay the clock for adjustment to changing photoperiods. In agreement with this hypothesis GABA activated or inhibited AME clock neurons, allowing for the distinction of three different GABA response types. Here, we examined which GABA receptors are responsible for these response types. We found that both ionotropic GABAA receptors and metabotropic GABAB receptors were expressed in AME clock cells. Via different signalling pathways, either one of them could account for all three GABA response types. The muscimol‐dependently activated GABAA receptor formed a chloride channel, while the SKF 97541‐dependently activated GABAB receptor signalled via G‐proteins, apparently targeting potassium channels. Expression of chloride exporters or importers determined whether GABAA receptor activation hyper‐ or depolarized AME neurons. For GABAB receptor responses second messenger gated channels present in the clock cells appeared to decide about the polarity of the GABA response. In summary, circadian clock neurons co‐expressed inhibitory and/or excitatory GABAA and GABAB receptors in various combinations, while cotransporter expression and the set of second messenger gated ion channels present allowed for distinct signalling in different clock neurons.