Functional role of astrocytes in neuronal sharp wave ripple oscillations

• Applicant: Dr. Ulrike Pannasch
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: Funded in 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 273734125

Synchronized activation of large numbers of neurons can result in neuronal network oscillations. Very prominent oscillatory activities of the hippocampus, the so-called sharp wave ripple oscillations, occur during rest and sleep. With their very fast time scale, at a frequency of 150-300Hz these oscillations are suitable for the induction of long-term potentiation and long-term depression. Although it is still unclear how large populations of neurons are synchronized, astroglial cells might be involved in the synchronization process. This assumption is based on the fact that one astrocyte is able to modulate the activity of up to 100.000 synapses of different neurons. Astroglial cells do not only fine tune neuronal excitability through the control of the extracellular potassium homeostasis but also uptake and release neuroactive substances modulating synaptic transmission. Astroglia might be able to synchronize the activity of particular neuronal assemblies because they are organized in communicating networks whose shape and extent correlates with that of neuronal functional units.To investigate whether astrocytes play a role in neuronal synchrony during oscillations, we will apply an interdisciplinary approach combining electrophysiology, calcium imaging and uncaging of neuro-and glia-active substances as well as electronmicroscopy. In the proposed project, we will elucidate if astrocytes sense and modulate sharp wave ripple oscillations through the recording of astroglial Ca2+ and current response as well as the targeted activation and inactivation of astrocytic networks during sharp wave ripples. We will furthermore examine whether they target particular neuronal ensembles or subpopulations by investigating astrocytes in different hippocampal areas and by using transgenic mice models enabling the identification of specific neuronal subtypes. Finally, we will examine whether specific neuron-glia interactions at the ultrastructural level are involved in the potential astroglial control of neuronal synchronization.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Dietmar Schmitz