Astrocyte Morphology Determines Properties Of Astroglial Networks

Alberto Pauletti1, Christian Henneberger2

1 Institute of Cellular Neurosciences, University of Bonn Medical School, Bonn, Germany.
2 Institute of Cellular Neurosciences, University of Bonn Medical School, Bonn, Germany. UCL Institute of Neurology, UCL, London, United Kingdom. German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Astrocytes form large networks throughout the brain. In the hippocampal CA1 region, astrocytes are connected by gap junctions that are mainly composed of GJα1 (connexin 43) and GJβ6 (connexin 30). Together, these proteins form a hexameric structure called connexons which can connect two adjacent cells by forming gap junctions. This astroglial gap junction coupling is important for various processes such as distribution of metabolites and regulation of synaptic transmission and plasticity. Previous experiments from our laboratory showed that induction of long-term potentiation and epileptiform activity rapidly changes the morphology of astrocyte and the diffusion within and between astrocytes in acute hippocampal slices. Therefore, we investigated the fundamental relationship between astrocytic structure and the strength of astroglial coupling using combinations of two-photon excitation fluorescence microscopy and electrophysiology. We found that the primary morphological determinant of coupling strength is the complexity of the astroglial branching pattern rather than the total intracellular volume available for diffusion. Using fluorescence recovery after photobleaching, we could also reveal that changes of intracellular diffusivity do not explain the link between astroglial morphological complexity and coupling. Moreover, we also showed, by analyzing the location and density of connexin 30 and 43, that the astrocyte structure does not define the pattern of gap junction formation between astrocytes. We are now investigating if a modifying astrocyte morphology using viral tools also modifies the connectivity within the astrocyte coupled network.