The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior.

The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior.
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DOI:
10.1371/journal.pbio.1000154
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发表时间:
2009-07
期刊:
影响因子:
9.8
通讯作者:
Allada R
Allada R
中科院分区:
生物学1区
文献类型:
--
作者:
Lear BC;Zhang L;Allada R

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动物使用不同的生物钟神经元来为早上和晚上的行为计时。本文揭示了果蝇早晨神经元和神经肽色素分散因子的直接神经靶点。生物钟神经元的离散集群在时间上组织日常行为,如睡眠和觉醒。在果蝇中,一个只有150个神经元的网络在早上和晚上驱动两个定时活动高峰。这些神经元的一个子集表达神经肽色素分散因子(PDF),这对于促进早晨行为以及在恒定条件下保持稳健的自由奔跑节律性非常重要。然而,PDF如何作用于下游回路来介导节律行为尚不清楚。使用PDF受体突变体的电路定向拯救,我们表明,PDF靶向仅1030个非PDF夜间昼夜节律神经元就足以驱动早晨行为。这种功能并不伴随着核心分子振荡器在明-暗条件下的大变化,表明PDF受体可能在这些条件下调节这些细胞的输出。我们发现,PDF还作用于这一集中的非PDF神经元,以调节晚上的活动阶段和周期长度,与核心振荡器的适度重置效应一致。PDF可能作用于更多分布的起搏神经元靶点,包括PDF神经元本身,以调节节律强度。在这里,我们揭示了PDF肽功能在昼夜节律行为中的电路图的定义特征,揭示了PDF的直接神经元靶点及其在这些位点的行为功能。这些研究定义了一个关键的直接输出电路足以多个PDF依赖的行为。动物依靠在一天中正确的时间醒来来寻找食物和配偶,并抵御捕食者。大脑中的昼夜节律起搏神经元在将特定行为定时到一天中的适当时间方面起着至关重要的作用。这些神经元进一步专门用于那些主要负责早晨和晚上行为的神经元。我们已经使用果蝇作为一个简单的模型系统来阐明定时的日常行为的重要神经回路。在果蝇中,一小群专门负责早晨行为的时钟神经元表达一种神经肽,即色素分散因子。到目前为止,还不清楚这种肽的直接神经靶点是什么,以及它在这些靶点上的作用如何介导定时行为。在这里,我们发现所谓的早晨时钟神经元直接与其他时钟神经元进行通信,这些神经元负责晚上的行为。这种沟通维持了高幅度的早晨活动,并在恒定的条件下设置了晚上活动的阶段以及活动节奏的周期。这些研究揭示了PDF函数在昼夜节律行为中的电路图。
Animals use distinct sets of clock neurons to time behaviors in the morning and evening. In this article, the direct neural targets for morning neurons and the neuropeptide pigment dispersing factor are revealed in the fruit fly. Discrete clusters of circadian clock neurons temporally organize daily behaviors such as sleep and wake. In Drosophila, a network of just 150 neurons drives two peaks of timed activity in the morning and evening. A subset of these neurons expresses the neuropeptide pigment dispersing factor (PDF), which is important for promoting morning behavior as well as maintaining robust free-running rhythmicity in constant conditions. Yet, how PDF acts on downstream circuits to mediate rhythmic behavior is unknown. Using circuit-directed rescue of PDF receptor mutants, we show that PDF targeting of just ∼30 non-PDF evening circadian neurons is sufficient to drive morning behavior. This function is not accompanied by large changes in core molecular oscillators in light-dark, indicating that PDF RECEPTOR likely regulates the output of these cells under these conditions. We find that PDF also acts on this focused set of non-PDF neurons to regulate both evening activity phase and period length, consistent with modest resetting effects on core oscillators. PDF likely acts on more distributed pacemaker neuron targets, including the PDF neurons themselves, to regulate rhythmic strength. Here we reveal defining features of the circuit-diagram for PDF peptide function in circadian behavior, revealing the direct neuronal targets of PDF as well as its behavioral functions at those sites. These studies define a key direct output circuit sufficient for multiple PDF dependent behaviors. Animals depend on being awake at the right time of day to find food and mates and fend off predators. Circadian pacemaker neurons in the brain play a crucial role in timing of specific behaviors to the appropriate times of day. These neurons are further specialized to those primarily responsible for morning and evening behavior. We have used the fruit fly Drosophila as a simple model system to elucidate the neural circuits important for timed daily behavior. In flies, a small group of clock neurons devoted to morning behavior express a neuropeptide, PIGMENT DISPERSING FACTOR (PDF). Until now it was unclear what the direct neural targets of this peptide are and how its actions at those targets mediate timed behavior. Here we find that the so-called morning clock neurons communicate directly to other clock neurons, those responsible for evening behavior. This communication sustains high amplitude morning activity and sets the phase of evening activity as well as the period of activity rhythms in constant conditions. These studies reveal the circuit diagram for PDF function in circadian behavior.
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