During corticogenesis, CajaI-Retzius (CR) neurons and radial gila participate in neuronal migration and the organization of radial columns of neurons. The complex circuitry among these interconnected columns provides the basis for the remarkable computational capacity of the cortex. Dysfunctional cortical circuits underlie a wide range of neurological and psychiatric disorders including epilepsy, mental retardation, schizophrenia, and dyslexia. However, we have very little understanding of how such specific circuits develop. We have recently found that radial glial cells divide to produce neurons that then migrate along their parent radial glial cell fiber into the developing cortex. This finding suggests that a radial glial 'mother' cell generates and guides daughter neurons throughout their development, and that in the mature brain the family of related, potentially interconnected neurons may underlie microciruits in the adult cerebral cortex. The proposed experiments will examine the hypotheses that radial gila provide pathways for neuronal regulation of neurogenesis and migration and that radial glial-derived cells may form functional radial units in the adult cortex. Clonally related cortical neurons will be labeled by transfecting rat neocortex in utero with a GFP-expressing replication-deficient retrovirus. The resulting GFP-expressing radial clones of pyramidal neurons can be visualized in living brain slices. We will use intracellular dye-filling, optical recording of calcium signals, and dual whole-cell recording to examine the functional significance of connectivity between radial gila and daughter neurons and within clones of related cells. Questions we plan to address include: Does coupling of migrating neurons to parental radial glia underlie neuronal migration? Are sibling neurons gap junction coupled to one another? Do lineage-related cell contacts determine the pattern of intracolumnar connectivity? Do CR cells and radial glia signal one another and does this signaling influence neurogenesis or migration?
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