Consolidation and maintenance of long-term memory involve dual functions of the developmental regulator Apterous in clock neurons and mushroom bodies in the Drosophila brain.
Consolidation and maintenance of long-term memory involve dual functions of the developmental regulator Apterous in clock neurons and mushroom bodies in the Drosophila brain.
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DOI：
10.1371/journal.pbio.3001459
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发表时间：
2021-12
期刊：
影响因子：
9.8
通讯作者：
Sakai T
中科院分区：
文献类型：
--
作者：
Inami S;Sato T;Kurata Y;Suzuki Y;Kitamoto T;Sakai T
记忆最初是不稳定的，但可以巩固为稳定的长期记忆（LTM），长期储存在大脑中。尽管最近取得了进展，但LTM有趣的神经生物学过程背后的分子和细胞机制仍然不完全清楚。使用果蝇求偶条件反射试验作为记忆范例，在这里，我们表明，LIM同源结构域（LIM-HD）转录因子Apterous（AP），这是已知的调节各种发育事件，所需的巩固和维护LTM。有趣的是，Ap通过不同的机制参与这两种记忆过程，在成年人大脑中的不同神经元亚群中。Ap及其辅因子Chip（Chi）是维持果蝇记忆中心蘑菇体（MB）LTM不可或缺的因子。另一方面，在含有色素分散因子（Pdf）的大腹外侧时钟神经元（LNvs）中，Ap以不依赖于Chi-independent的方式在记忆巩固中起着至关重要的作用，LNvs调节行为唤醒和睡眠。由于中断的神经传递和电沉默的时钟神经元损害记忆巩固，Ap的建议，以确保兴奋性的LNvs的记忆的稳定。事实上，离体成像显示，Ap而不是Chi的功能降低，导致对l-LNv中抑制性神经递质γ-氨基丁酸（GABA）的Cl−反应放大，表明野生型（WT）Ap通过抑制GABA反应保持高l-LNv兴奋性。因此，通过敲低GABAA受体来增强l-LNvs的兴奋性补偿了ap无效突变体中受损的记忆巩固。总的来说，我们的研究结果揭示了独特的双重功能的发展调节剂Ap的LTM巩固时钟神经元和LTM维护MB。一项使用果蝇的神经遗传学研究表明，中枢表达的LIM同源结构域转录因子Apterous在两种不同的记忆过程中起着关键的神经元类型依赖性作用-巩固和维持长期记忆。
Memory is initially labile but can be consolidated into stable long-term memory (LTM) that is stored in the brain for extended periods. Despite recent progress, the molecular and cellular mechanisms underlying the intriguing neurobiological processes of LTM remain incompletely understood. Using the Drosophila courtship conditioning assay as a memory paradigm, here, we show that the LIM homeodomain (LIM-HD) transcription factor Apterous (Ap), which is known to regulate various developmental events, is required for both the consolidation and maintenance of LTM. Interestingly, Ap is involved in these 2 memory processes through distinct mechanisms in different neuronal subsets in the adult brain. Ap and its cofactor Chip (Chi) are indispensable for LTM maintenance in the Drosophila memory center, the mushroom bodies (MBs). On the other hand, Ap plays a crucial role in memory consolidation in a Chi-independent manner in pigment dispersing factor (Pdf)-containing large ventral–lateral clock neurons (l-LNvs) that modulate behavioral arousal and sleep. Since disrupted neurotransmission and electrical silencing in clock neurons impair memory consolidation, Ap is suggested to contribute to the stabilization of memory by ensuring the excitability of l-LNvs. Indeed, ex vivo imaging revealed that a reduced function of Ap, but not Chi, results in exaggerated Cl− responses to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in l-LNvs, indicating that wild-type (WT) Ap maintains high l-LNv excitability by suppressing the GABA response. Consistently, enhancing the excitability of l-LNvs by knocking down GABAA receptors compensates for the impaired memory consolidation in ap null mutants. Overall, our results revealed unique dual functions of the developmental regulator Ap for LTM consolidation in clock neurons and LTM maintenance in MBs. A neurogenetic study using Drosophila reveals that the centrally expressed LIM-homeodomain transcription factor Apterous plays a crucial neuron-type-dependent role in two different memory processes - consolidation and maintenance of long-term memory.