Multiple Signaling Pathways Coordinately Regulate Forgetting of Olfactory Adaptation through Control of Sensory Responses in Caenorhabditis elegans
Multiple Signaling Pathways Coordinately Regulate Forgetting of Olfactory Adaptation through Control of Sensory Responses in Caenorhabditis elegans
复制标题
DOI：
10.1523/jneurosci.0031-17.2017
复制
发表时间：
2017-10-18
影响因子：
5.3
通讯作者：
Ishihara, Takeshi
中科院分区：
文献类型：
--
作者：
Kitazono, Tomohiro;Hara-Kuge, Sayuri;Ishihara, Takeshi
遗忘记忆对于动物正确应对不断变化的环境至关重要。为了阐明遗忘的机制，我们使用了秀丽隐杆线虫雌雄同体的行为可塑性之一，嗅觉适应一种有吸引力的气味，双乙酰，作为一个简单的学习模型。In C.在线虫中，TIR-1/JNK-1通路通过促进AWC感觉神经元的神经分泌来加速嗅觉适应的遗忘。在这项研究中，为了确定TIR-1/JNK-1通路的下游效应子，我们对TIR-1（ok 1052）的功能获得性突变体的抑制子进行了遗传筛选，该突变体表现出过度遗忘。我们的筛选表明，三种蛋白质-膜蛋白，MACO-1，受体酪氨酸激酶，SCD-2，和它的假定配体，HEN-1-调节遗忘的TIR-1/JNK-1途径的下游。我们进一步证明了MACO-1和SCD-2/HEN-1在平行的遗传通路中起作用，并且只有MACO-1调节对异戊醇的嗅觉适应的遗忘，异戊醇是一种由不同类型的感觉神经元感知的有吸引力的气味。在嗅觉适应中，嗅觉神经元中气味诱发的Ca 2+反应通过条件反射减弱，然后恢复。Ca 2+成像研究显示，这种衰减在maco-1和scd-2突变动物中比在野生型动物如TIR-1/JNK-1途径突变体中持续更长时间。此外，组胺门控氯离子通道的时间沉默揭示了条件反射后AWC神经元的神经元活性对于正确的遗忘是重要的。我们提出，不同的信号通路，其中每一个都有一个特定的功能，可以协调和时间调节遗忘通过控制感官反应。
Forgetting memories is important for animals to properly respond to continuously changing environments. To elucidate the mechanisms of forgetting, we used one of the behavioral plasticities of Caenorhabditis elegans hermaphrodite, olfactory adaptation to an attractive odorant, diacetyl, as a simple model of learning. In C. elegans, the TIR-1/JNK-1 pathway accelerates forgetting of olfactory adaptation by facilitating neural secretion from AWC sensory neurons. In this study, to identify the downstream effectors of the TIR-1/JNK-1 pathway, we conducted a genetic screen for suppressors of the gain-of-function mutant of tir-1 (ok1052), which shows excessive forgetting. Our screening showed that three proteins-a membrane protein, MACO-1; a receptor tyrosine kinase, SCD-2; and its putative ligand, HEN-1-regulated forgetting downstream of the TIR-1/JNK-1 pathway. We further demonstrated that MACO-1 and SCD-2/HEN-1 functioned in parallel genetic pathways, and only MACO-1 regulated forgetting of olfactory adaptation to isoamyl alcohol, which is an attractive odorant sensed by different types of sensory neurons. In olfactory adaptation, odor-evoked Ca2+ responses in olfactory neurons are attenuated by conditioning and recovered thereafter. A Ca2+ imaging study revealed that this attenuation is sustained longer in maco-1 and scd-2 mutant animals than in wild-type animals like the TIR-1/JNK-1 pathway mutants. Furthermore, temporal silencing by histamine-gated chloride channels revealed that the neuronal activity of AWC neurons after conditioning is important for proper forgetting. We propose that distinct signaling pathways, each of which has a specific function, may coordinately and temporally regulate forgetting by controlling sensory responses.