Different populations of dorsal lateral geniculate nucleus neurons have concentration-specific requirements for a...

A macromolecular fraction of conditioned culture medium (CM) derived from explant cocultures of embryonic rat posterior cortex and caudal thalamus is able to support the survival of neurons in the dorsal lateral geniculate nucleus (dLGN) of newborn rats following ablation of dLGN cortical target areas. In the present study we tested whether the survival-promoting activity of this target-derived neurotrophic agent was concentration dependent and whether different subpopulations of dLGN neurons were equally responsive. With the starting concentration of the CM fraction designated X, increasing concentration results in a progressive falloff in trophic activity so that at 200X overall dLGN survival is similar to that seen in unconditioned medium (UM) controls. In contrast, diluting the fraction produces an increase in activity until maximal survival is achieved at 0.2X. Further dilutions result in a decline in trophic activity until control values are reached at 0.001X. Two populations of neurons within the dLGN, defined by their time of origin, respond in a specific manner to the different concentrations. Neurons generated during the early stages of neurogenesis (E14) have maximal survival (25.8%) at 0.05X, whereas those neurons generated later (E15/16) are maximally supported (30.7% survival) at 10X, a 200-fold difference in concentration. While it is possible that separate neurotrophic and neurotoxic molecules exist for each of these populations of dLGN neurons, the most parsimonious interpretation of the data is that a single cortically derived neurotrophic factor exists whose production is strictly controlled during development to achieve maximal effect on different populations of thalamic neurons that may be functionally distinct.