NGF facilitates the developmental maturation of the previously committed cholinergic interneurons in the striatal matrix

Abstract

Although all of the cholinergic interneurons of the striatum are generated early in development, the maturation of these neurons depends on striatal compartmental localization. The majority of the cholinergic neurons in the patches turn on choline acetyltransferase (CHAT) embryonically, whereas the majority of cholinergic neurons in the matrix turn on CHAT postnatally. To determine whether CHAT expression can be induced earlier in the cholinergic neurons and whether the facilitation is compartment specific, we infused nerve growth factor (NGF) in the lateral ventricle of either embryonic day 19 embryos or postnatal day 1 pups. We simultaneously marked the patch compartment by injecting the retrograde fluorescent tracer True Blue into the substantia nigra at the times of the NGF infusions. After a 2- day survival time, NGF induced a dramatic increase in the number of CHAT- immunoreactive neurons in the matrix compartment (up to adult levels), whereas the NGF infusions did not increase the number of CHAT neurons in the patch compartment. Analyses of the compartmental distributions of the p75 and trkA NGF receptors themselves do not provide an explanation for the differential cholinergic maturation in the compartments of the control striatum or for the upregulation of CHAT in the striatal matrix after the NGF infusion. We conclude that NGF infusion is capable of facilitating the normally slow cholinergic maturation of the cholinergic neurons in the matrix, whereas the cholinergic maturation of the CHAT cells in the patch compartment seems to be largely independent of NGF signalling.