DIFFERENTIAL MODULATION OF THE CHOLINERGIC ACTIVITY OF RAT CNS NEURONS IN CULTURE

Treatment of septal cultures prepared from 17-day-old embryos with two different antimitotic agents, cytosine arabinoside (ara C) and 5'-fluoro-2'-deoxyuridine (FUdR), caused a 2-fold increase in the level of choline acetyltransferase (CAT) activity and no change in glutamic acid decarboxylase (GAD) activity. In these cultures, there was also a large decrease in the number of astrocytes as determined by immunofluorescence for glial fibrillary acidic protein (GFAP). Furthermore, when epidermal growth factor (EGF) was added to the septal cultures to increase the astrocyte population, the CAT activity decreased. Therefore, it would appear that the astrocytes are responsible for producing this down-regulation on cholinergic neurons. In order to determine whether all CNS cholinergic neurons can be inhibited in this manner, cultures were prepared from two other CNS regions that contain a high percentage of cholinergic neurons, i.e. the striatum and the ventral spinal cord. When these cultures were treated with the antimitotic agents, there was little modification of the CAT or GAD activities. These results suggest that the astrocytic microenvironment of the septal neurons exerts an inhibitory effect on the CAT activity either via a soluble factor or via cell-cell contact. Such studies are an important demonstration that non-neuronal cells may alter cholinergic properties during CNS development.