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

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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.