Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour.
Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour.
复制标题
DOI：
10.1038/nature20145
复制
发表时间：
2016-11-17
期刊：
影响因子：
64.8
通讯作者：
Freeman, Marc R.
中科院分区：
文献类型：
--
作者：
Ma, Zhiguo;Stork, Tobias;Bergles, Dwight E.;Freeman, Marc R.
星形胶质细胞与整个大脑中的突触联系在一起，并表达神经递质受体，这种受体可以提高细胞内钙离子(Ca~(2+))。星形胶质细胞钙信号被认为是调节神经回路活动的信号，但调控这些事件的途径还不清楚，体内证据表明星形胶质细胞钙离子的变化与神经传递或行为的变化有关。在这里，我们展示了果蝇星形胶质细胞在活体内表现出活性调节的钙信号事件。从Tdc2+神经元释放的酪胺(Tyr)和章鱼胺(Oct)通过八胺酪胺受体(Oct-TyrR)和Trp通道沃特维奇(Wtrw)直接向星形胶质细胞发出信号，刺激钙离子增加，而星形胶质细胞反过来调节下游的多巴胺(DA)神经元。在活体制剂中应用TYR或OCT可使多巴胺(DA)神经元沉默，这种抑制需要星形细胞的OCT-TyrR和WTRW。星形胶质细胞钙信号的增加足以抑制DA神经元的活动，这是由星形胶质细胞的内吞功能和腺苷受体介导的。选择性阻断OCT-TyrR或Wtrw在星形胶质细胞中的表达可阻断星形胶质细胞的钙信号，并深刻改变嗅觉驱动的趋化行为和触摸诱导的惊吓反应。我们的工作确定OCT-TyrR和Wtrw是星形胶质细胞钙信号机制的关键组成部分，提供了直接证据表明基于OCT和Tyr的神经调节可以由星形胶质细胞介导，并表明星形胶质细胞在多种感觉驱动的行为中是必不可少的。
Astrocytes associate with synapses throughout the brain and express receptors for neurotransmitters that can elevate intracellular calcium (Ca2+) . Astrocyte Ca2+ signaling has been proposed to modulate neural circuit activity , but pathways regulating these events are poorly defined and in vivo evidence linking changes in astrocyte Ca2+ to alterations in neurotransmission or behaviors is limited. Here we show Drosophila astrocytes exhibit activity-regulated Ca2+ signaling events in vivo. Tyramine (Tyr) and octopamine (Oct) released from Tdc2+ neurons signal directly to astrocytes to stimulate Ca2+ increases through the octopamine-tyramine receptor (Oct-TyrR) and the TRP channel Waterwitch (Wtrw), and astrocytes in turn modulate downstream dopaminergic (DA) neurons. Tyr or Oct application to live preparations silenced dopaminergic (DA) neurons and this inhibition required astrocytic Oct-TyrR and Wtrw. Increasing astrocyte Ca2+ signaling was sufficient to silence DA neuron activity, which was mediated by astrocyte endocytic function and adenosine receptors. Selective disruption of Oct-TyrR or Wtrw expression in astrocytes blocked astrocyte Ca2+ signaling and profoundly altered olfactory-driven chemotaxis behavior and touch-induced startle responses. Our work identifies Oct-TyrR and Wtrw as key components of the astrocyte Ca2+ signaling machinery, provides direct evidence that Oct- and Tyr-based neuromodulation can be mediated by astrocytes, and demonstrates that astrocytes are essential for multiple sensory-driven behaviors.
登录
查看更多内容
DOI：
10.1083/jcb.150.2.f83
发表时间：
2000-07-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Brody T;Cravchik A
通讯作者：
Cravchik A
影响因子：
11.4
作者：
SAUDOU, F;AMLAIKY, N;HEN, R
通讯作者：
HEN, R
DOI：
10.1002/neu.20053
发表时间：
2005-01-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Nitabach, MN;Sheeba, V;Holmes, TC
通讯作者：
Holmes, TC
影响因子：
6.2
作者：
FATATIS, A;RUSSELL, JT
通讯作者：
RUSSELL, JT
来自IP3R2（ - / - ）小鼠的星形胶质细胞中的Ca（2+）脑切片中的CA（2+）信号传导。
影响因子：
25
作者：
Srinivasan, Rahul;Huang, Ben S.;Venugopal, Sharmila;Johnston, April D.;Chai, Hua;Zeng, Hongkui;Golshani, Peyman;Khakh, Baljit S.
通讯作者：
Khakh, Baljit S.