Lateral axonal modulation is required for stimulus-specific olfactory conditioning in Drosophila.
Lateral axonal modulation is required for stimulus-specific olfactory conditioning in Drosophila.
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DOI：
10.1016/j.cub.2022.09.007
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发表时间：
2022-10-24
期刊：
影响因子：
9.2
通讯作者：
Parnas, Moshe
中科院分区：
文献类型：
--
作者：
Manoim, Julia E.;Davidson, Andrew M.;Weiss, Shirley;Hige, Toshihide;Parnas, Moshe
有效且针对特定刺激的学习对于动物的生存至关重要。已知有两种主要机制可以帮助联想学习的刺激特异性。一是神经元中准确的刺激特异性表征。第二个是增强信号在感觉刺激后诱导神经调节的有限有效时间窗口。然而，这些机制在防止非特异性关联方面往往并不完善；不同的感觉刺激可以由重叠的神经元群来表示，更重要的是，即使没有同时发生的感觉诱发神经元活动，单独的增强信号也可以诱导神经调节。在这里，我们报告了一种关键的神经调节机制，它可以抵消这两种限制，因此对于学习的刺激特异性至关重要。在果蝇中，嗅觉信号由胆碱能凯尼恩细胞（KC）稀疏地表示，该细胞接收多巴胺能增强输入。我们发现 KC 具有许多由毒蕈碱 B 型受体 (mAChR-B) 介导的轴突连接。通过使用功能成像和光遗传学方法，我们表明这些轴突连接抑制邻近 KC 中气味诱发的钙反应和多巴胺诱发的 cAMP 信号。引人注目的是，行为实验表明，KC 中的 mAChR-B 敲低会导致与强化剂无关的气味价态发生不良变化，从而损害嗅觉学习。因此，这种局部神经调节与稀疏的感觉表征和全局多巴胺能调节协同作用，以实现有效且准确的记忆形成。马诺伊姆等人。研究表明，果蝇蘑菇体中凯尼恩细胞之间丰富的轴突突触是由毒蕈碱 B 型受体介导的，该受体抑制邻近细胞中的 Ca2+ 和 cAMP 信号。由于这两个信号对于突触可塑性至关重要，因此横向抑制增强了联想学习的刺激特异性。
Effective and stimulus-specific learning is essential for animals’ survival. Two major mechanisms are known to aid stimulus specificity of associative learning. One is accurate stimulus-specific representations in neurons. The second is a limited effective temporal window for the reinforcing signals to induce neuromodulation after sensory stimuli. However, these mechanisms are often imperfect in preventing unspecific associations; different sensory stimuli can be represented by overlapping populations of neurons, and more importantly, the reinforcing signals alone can induce neuromodulation even without coincident sensory-evoked neuronal activity. Here we report a crucial neuromodulatory mechanism that counteracts both limitations and is thereby essential for stimulus specificity of learning. In Drosophila, olfactory signals are sparsely represented by cholinergic Kenyon cells (KCs), which receive dopaminergic reinforcing input. We find that KCs have numerous axo-axonic connections mediated by the muscarinic type-B receptor (mAChR-B). By using functional imaging and optogenetic approaches, we show that these axo-axonic connections suppress both odor-evoked calcium responses and dopamine-evoked cAMP signals in neighboring KCs. Strikingly, behavior experiments demonstrate that mAChR-B knockdown in KCs impairs olfactory learning by inducing undesired changes to the valence of an odor that was not associated with the reinforcer. Thus, this local neuromodulation acts in concert with sparse sensory representations and global dopaminergic modulation to achieve effective and accurate memory formation. Manoim et al. show that the abundant axo-axonic synapses between Kenyon cells in Drosophila mushroom body are mediated by muscarinic type-B receptors, which suppress Ca2+ and cAMP signals in neighboring cells. Since both signals are essential for synaptic plasticity, the lateral suppression enhances the stimulus specificity of associative learning.
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影响因子：
7.3
作者：
Hackley CR;Mazzoni EO;Blau J
通讯作者：
Blau J
影响因子：
64.5
作者：
Davie K;Janssens J;Koldere D;De Waegeneer M;Pech U;Kreft Ł;Aibar S;Makhzami S;Christiaens V;Bravo González-Blas C;Poovathingal S;Hulselmans G;Spanier KI;Moerman T;Vanspauwen B;Geurs S;Voet T;Lammertyn J;Thienpont B;Liu S;Konstantinides N;Fiers M;Verstreken P;Aerts S
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影响因子：
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作者：
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通讯作者：
Rubin GM
影响因子：
7.7
作者：
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影响因子：
7.3
作者：
Akk, G;Auerbach, A
通讯作者：
Auerbach, A