ASTROCYTE ORIGINS SHAPE REGIONAL NEURAL NETWORK IDENTITY

Precise development of neural networks relies upon intricate organization within and across brain regions. In this framework, astrocytes play pivotal roles orchestrating formation of nascent circuitry. Through direct and indirect contact with neurons, astrocytes engulf synapses, mediate plasticity, and contribute to neurogenesis. Furthermore, astrocytes have been shown to induce formation and stabilization of synaptic contacts, and hypothesized to be responsible for specification of the synapse. Our group has previously highlighted the transcriptional differences between astrocytes and neurons across brain areas. Building upon these findings, we hypothesized that region-specific transcriptomic profiles underpin distinct activity patterns within developing networks. We discovered intrinsic properties defined by brain region in astrocytes are sufficient to modulate developing neuronal networks in cocultures comprised of neurons and astrocytes from diverse brain regions. Notably, calcium activity in matching cocultures from the thalamus exhibits inherent differences compared to those from the cortex. However, this distinctive phenotype changes when astrocytes and neurons from both regions are mismatched, showing a bias towards the region from which the astrocytes originated. Additionally, we observed region-specific phenotypes in cell morphology and expression of specific synaptic markers are reliant on the brain region from which the astrocytes are isolated, and determined these phenotypes are reproducible using conditioned media from regionalized astrocytes. Lastly, we have injected foreign astrocytes into the cortex to determine if these phenotypes are reproducible in vivo. Further investigation will elucidate underlying mechanisms responsible for regional specialization of neural networks, ultimately highlighting an emerging role of astrocytic contribution to brain region specification.