GROWTH-PROMOTING INTERACTIONS BETWEEN THE MURINE NEOCORTEX AND THALAMUS IN ORGANOTYPIC COCULTURES

The aim of this study was to assess whether developing cerebral cortex produces diffusible factors that can affect the growth of thalamic ce lls and, if so, what the role of these factors might be during the for mation of thalamocortical connections. We studied interactions between cultured organotypic explants from mice maintained in defined serum-f ree medium. First, we cultured explants of embryonic dorsolateral thal amus in isolation from any other tissue; after culture, these explants were viewed intact and then sectioned. We estimated the numbers of he althy and pyknotic cells before and after culture, and the rates of mi tosis in the explants during culture (using bromodeoxyuridine). Based on these data, we concluded that the majority of cells in the thalamic explants survived, although significant numbers of pyknotic cells did accumulate. Thalamic explants extended either very few or no neurites when cultured alone. We then cultured explants of embryonic thalamus near to explants from other tissues. A gap was always maintained betwe en the explants, and we measured the length and density of neurite out growth from each thalamic explant. Slices of embryonic cortex promoted a small but significant increase in the amount of growth from thalami c explants. Postnatal cortex stimulated much more profuse neurite outg rowth; postnatal cerebellum had less of an effect, and postnatal medul la or liver had none. We showed that there was significantly more outg rowth from thalamic explants cultured in medium that had been precondi tioned with cortical slices than from thalamic explants cultured in co ntrol medium, confirming that diffusible factors were produced by the cortex. The survival and mitotic rates of thalamic cells were unaffect ed by co-culture with the cortex. We conclude that the developing cort ex releases diffusible factors that stimulate the growth of thalamic n eurites and that other regions of the brain may also release the same substance(s). The lack of a specific source of thalamic growth promoti ng factor(s) argues against a role for these factors in guiding thalam ic axons to specific targets; indeed, we were unable to demonstrate an y chemotropic guidance of thalamic axons towards cortical explants in collagen gels. Since postnatal cortex has a more potent stimulatory ef fect than prenatal cortex, it seems possible that, in vivo, the cortic al-derived factors act mainly on thalamocortical axons that have locat ed their targets and are in the process of arborizing and refining the ir connections.