During the embryonic period, neurons are generated by a sequence of successive cell divisions which occur in the ventricular zone, a zone lining the ventricles. In some species like the ferret, neurogenesis continues through into the early postnatal period. The factors that control cell divisions are largely unknown. Recent evidence suggests that in the mammalian neocortex the neurotransmitters GABA and glutamate play an important role by inhibiting the rate at which cells are born in the mammalian neocortex. Another transmitter-like substance is adenosine. Because adenosine is known to have mitogenic effects in non-neuronal cells, my project involved 2 major experiments, in which I tested the hypothesis that adenosine might be involved in cortical neurogenesis. In the first experiment, I conducted in vitro studies in which organotypic slices of posterior neocortex between postnatal day 1 and 4 were cultured in the presence or absence of adenosine in the medium. The data show that adenosine application leads to a significant increase in the number of newborn cells compared to cultures in which no adenosine had been added. In a second series of experiments, I employed calcium imaging techniques to determine whether adenosine can stimulate cells in the ventricular zone. Optical recording techniques using the calcium indicator dyes fluo-3 or fura-2 confirmed the presence of adenosine-responsive cells in the ferret ventricular zone and revealed an increase in the number of cells with adenosine receptors during embryonic and early postnatal development. Taken together, the data show that adenosine may be an important transmitter-like molecule that, like GABA and glutamate, influences corticogenesis.
