The role of P2Y1 and AMPA receptors in astrocyte plasticity

• Applicant: Professor Dr. Christian Lohr
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 279354007

Perisynaptic astrocytes sense neurotransmitters released from presynaptic terminals and respond with calcium signalling by activation of a multitude of receptors such metabotropic and ionotropic glutamate receptors as well as purinoceptors. Calcium signalling in astrocytes triggers the release of gliotransmitters which are supposed to be involved in synaptic plasticity. In the proposed project we aim to elucidate the contribution of astrocytic glutamatergic and purinergic receptors to the spatio-temporal pattern of astrocyte calcium signalling and to astrocyte plasticity. We hypothesis that: a) Metabotropic and ionotropic glutamate receptors as well as P2Y1 purinoceptors mediate different patterns of local and global calcium signalling in astrocytes, b) Neuron-astrocyte signalling undergoes synaptic plasticity upon tetanic stimulation. To address these hypotheses, we employ transgenic mice carrying astrocyte-specific deletion of AMPA and P2Y1 receptors, respectively. We combine these astrocyte-specific transgenes with laser-guided stimulation techniques such as photoactivation of caged calcium and IP3, respectively, to assess the effect of astrocyte-specific stimulation on astrocyte plasticity and neuronal performance. We use the mouse olfactory bulb as model system, because the olfactory bulb can be used as a whole, i.e. with intact neuronal circuits in contrast to brain slices of, e.g., the hippocampus. In addition, the olfactory bulb contains cell body-free synaptic domains in so-called glomeruli, invaded by clearly visible astrocyte processes, rendering the system ideal for imaging studies on astrocytes. The results will broaden our understanding how astrocytes are implemented in neuronal networks and influence neuronal performance such as odour perception. They will demonstrate that astrocytes are by no means passive elements of the brain serving solely homeostatic functions, but significantly contribute to information processing and hence brain function.

• DFG Programme: Research Grants