Control of neuronal activity by the co-transmitter ATP: Role of P2Y1 receptors

在嗅球的嘌呤能递质系统的蛋白质的显着表达表明，这一信号通路在处理气味信息的重要作用。然而，ATP及其代谢产物如何影响该脑区的神经元信号传导尚不清楚。最近，我们的小组可以证明，ATP作为共同递质与谷氨酸一起由感觉神经元释放，激活神经胶质细胞。此外，通过光解释放笼状核苷酸，我们可以表明，ATP调节嗅球神经元信号转导的第一次。模拟生理释放的ATP的光解释放导致通过P2Y1受体调节神经元网络的自发活动。在拟议的项目中，ATP对神经网络的影响将被详细揭示。功能性表达P2Y1受体的神经元将使用来自笼状化合物的ATP的光解释放结合膜片钳记录和共聚焦钙成像来鉴定。我们的初步工作表明，嗅觉神经元，如二尖瓣细胞或外部簇状细胞，这是必不可少的气味信息处理，是ATP的目标。我们的目的是阐明G蛋白偶联的P2Y1受体的激活控制神经元兴奋性的细胞和分子机制。此外，我们将研究如何内源性释放ATP刺激这嘌呤信号通路，通过使用传入（嘌呤）轴突的电刺激。我们期待新的见解嘌呤能系统影响嗅球神经元的性能，以及如何调节气味信息处理的机制。

The pronounced expression of proteins of the purinergic transmitter system in the olfactory bulb suggests an important role of this signalling pathway in the processing of odour information. Yet, how ATP and its metabolites affect neuronal signalling in this brain region is not known. Recently, our group could demonstrate that ATP is released as co-transmitter together with glutamate by sensory neurons, activating glial cells. Furthermore, by means of photolytic release of caged nucleotides, we could show for the first time that ATP modulates neuronal signal transduction in the olfactory bulb. Photolytic release of ATP, mimicking the physiological release, results in the modulation of spontaneous activity of the neuronal network via P2Y1 receptors. In the proposed project, the impact of ATP on the neuronal network will be unravelled in detail. Neurons that functionally express P2Y1 receptors will be identified using photolytic release of ATP from caged compounds in combination with patch-clamp recordings and confocal calcium imaging. Our preliminary work suggests that glutamatergic neurons such as mitral cells or external tufted cells, which are essential for odour information processing, are the targets of ATP. It is our aim to elucidate the cellular and molecular mechanisms by which the activation of G-protein-coupled P2Y1 receptors controls the excitability of the neurons. In addition, we will study how endogenously released ATP stimulates this purinergic signalling pathway by using electrical stimulation of afferent (purinergic) axons. We expect new insights into the mechanisms by which the purinergic system affects neuronal performance in the olfactory bulb, and how this modulates odour information processing.