Emerging Roles of Astrocytes in CNS

PL1 Emerging Roles of Astrocytes in CNS ○Maiken Nedergaard1 University of Rochester Medical Center1 The last 20 years have witnessed a dramatic departure from the classical thinking: neurons are no longer believed to be the sole substrate of higher brain function and deciphering the role of neuroglia as active contributors to coordinated network activity has emerged as an exciting frontier in the study of neuroscience. One popular model known as the “tripartite synapse” suggests that astrocytes, which extend processes that ensheathe neuronal synapses, detect the release of neurotransmitters and actively modulate pre- and post-synaptic neurotransmission by the calcium dependent release of “gliotransmitters” (i.e. transmitters released from glial cells that facilitate communication between neurons and other glia). However, recent evidence that astrocytes undergo developmental regulation of receptors sensitive to glutamatergic neurotransmission, and thus do not express receptors (e.g. mGluR5) thought to mediate gliotransmitter release in the adult brain, have questioned this model. Additionally, the functional significance of gliotransmission remains unclear due to the non-physiological nature of many of the experiments that gave rise to the concept. Astrocytes during evolution have expanded in parallel with increasing complexity of brain processing. To test the idea that human astrocytes contribute to the extraordinary computational power of the human brain, we have recently generated humanized chimeric mice by engrafting human glia progenitor cells in young pups. As the mice grow up, a large proportion of mouse astrocytes are replaced with human astrocytes. Remarkably, the human astrocytes distributed evenly, organized in non-overlapping domains, and maintained their large dimensions compared with host astrocytes. We further observed that the adult chimeric mice are faster learners in an array of behavioral test, including fear conditioning, Barnes Maze, and novel object recognition (Cell Stem Cell, 2013). Finally, the importance of the macroscopic clearance system ? the glia-lymphatics will be discussed (Science Translational Medicine, 2012)

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