Reciprocal cholinergic and GABAergic modulation of the small ventrolateral pacemaker neurons of Drosophila's circadian clock neuron network
Reciprocal cholinergic and GABAergic modulation of the small ventrolateral pacemaker neurons of Drosophila's circadian clock neuron network
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DOI：
10.1152/jn.00931.2011
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发表时间：
2012-04-01
影响因子：
2.5
通讯作者：
Shafer, Orie T.
中科院分区：
文献类型：
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作者：
Lelito, Katherine R.;Shafer, Orie T.
Lelito KR，Shafer OT.果蝇昼夜节律神经元网络中小的腹外侧型起搏神经元的胆碱能和GABA能相互调节。《神经生理学杂志》107：2096-2108,2012。2012年1月25日首次出版；doi：10.1152/jn.00931.2011。-相对简单的果蝇时钟神经元网络是一个有价值的昼夜节律神经元基础的模型系统。不幸的是，该网络的许多关键神经元类别无法进行电生理分析。因此，我们采用了基因编码的传感器来解决苍蝇生物钟网络的生理问题。用基因编码的Ca~(2+)和cAMP传感器，我们研究了两类特殊的时钟神经元，大的和小的腹外侧神经元(L和S-LN(V)S)对与其调制有关的两种神经递质：乙酰胆碱(ACh)和γ-氨基丁酸(GABA)的生理反应。L-LNV对胆碱能激动剂和GABA应用的cAMP和Ca~(2+)动态的实时成像与已发表的电生理数据吻合良好，表明我们的传感器能够在单个成年时钟神经元胞体内忠实地报告对这些递质的急性生理反应。我们将这些实时成像方法扩展到S-LN(V)S，这是一种关键的神经元起搏器，其在成人大脑中的生理特性在很大程度上尚不清楚。我们的S-LNV实验揭示了对沐浴胆碱能激动剂的兴奋反应和GABA的抑制效应，并证实ACh和GABA的拮抗作用扩展到对cAMP信号的影响。这些数据支持最近发表的但未经生理测试的S-LNV调制模型，并导致预测S-LN(V)S的胆碱能和GABA能输入将对这些关键起搏神经元内的分子时钟的相位和/或周期产生相反的影响。
Lelito KR, Shafer OT. Reciprocal cholinergic and GABAergic modulation of the small ventrolateral pacemaker neurons of Drosophila's circadian clock neuron network. J Neurophysiol 107: 2096-2108, 2012. First published January 25, 2012; doi:10.1152/jn.00931.2011.-The relatively simple clock neuron network of Drosophila is a valuable model system for the neuronal basis of circadian timekeeping. Unfortunately, many key neuronal classes of this network are inaccessible to electrophysiological analysis. We have therefore adopted the use of genetically encoded sensors to address the physiology of the fly's circadian clock network. Using genetically encoded Ca2+ and cAMP sensors, we have investigated the physiological responses of two specific classes of clock neuron, the large and small ventrolateral neurons (l-and s-LN(v)s), to two neurotransmitters implicated in their modulation: acetylcholine (ACh) and gamma-aminobutyric acid (GABA). Live imaging of l-LNv cAMP and Ca2+ dynamics in response to cholinergic agonist and GABA application were well aligned with published electrophysiological data, indicating that our sensors were capable of faithfully reporting acute physiological responses to these transmitters within single adult clock neuron soma. We extended these live imaging methods to s-LN(v)s, critical neuronal pacemakers whose physiological properties in the adult brain are largely unknown. Our s-LNv experiments revealed the predicted excitatory responses to bath-applied cholinergic agonists and the predicted inhibitory effects of GABA and established that the antagonism of ACh and GABA extends to their effects on cAMP signaling. These data support recently published but physiologically untested models of s-LNv modulation and lead to the prediction that cholinergic and GABAergic inputs to s-LN(v)s will have opposing effects on the phase and/or period of the molecular clock within these critical pacemaker neurons.