A miniaturized nigrostriatal-like circuit regulating locomotor performance in a protochordate

To gain insight into the evolution of motor control systems at the origin of vertebrates, we have investigated higher-order motor circuitry in the protochordate Oikopleura dioica. We have identified a highly miniaturized circuit in Oikopleura with a projection from a single pair of dopaminergic neurons to a small set of synaptically coupled GABAergic neurons, which in turn exert a disinhibitory descending projection onto the locomotor central pattern generator. The circuit is reminiscent of the nigrostriatopallidal system in the vertebrate basal ganglia, in which disinhibitory circuits release specific movements under the modulatory control of dopamine. We demonstrate further that dopamine is required to optimize locomotor performance in Oikopleura, mirroring its role in vertebrates. A dopamine-regulated disinhibitory locomotor control circuit reminiscent of the vertebrate nigrostriatopallidal system was thus already present at the origin of ancestral chordates and has been maintained in the face of extreme nervous system miniaturization in the urochordate lineage.publishedVersio

A human iPSC-astroglia neurodevelopmental model reveals divergent transcriptomic patterns in schizophrenia

Abstract While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In the present study, we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental stages critical for SCZ using RNA sequencing. The model generated astrocyte-specific gene expression patterns during differentiation that corresponded well to astroglia-specific expression signatures of in vivo cortical fetal development. Using this model we identified SCZ-specific expression dynamics, and found that SCZ-associated differentially expressed genes were significantly enriched in the medial prefrontal cortex, striatum, and temporal lobe, targeting VWA5A and ADAMTS19 . In addition, SCZ astrocytes displayed alterations in calcium signaling, and significantly decreased glutamate uptake and metalloproteinase activity relative to controls. These results implicate novel transcriptional dynamics in astrocyte differentiation in SCZ together with functional changes that are potentially important biological components of SCZ pathology