EXPRESSION OF NEURONAL-NOS IN DEVELOPING BASAL FOREBRAIN CHOLINERGIC NEURONS - REGULATION BY NGF

Nerve growth factor (NGF) acts through the receptor tyrosine kinase tr kA to serve as a trophic factor for cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band. We have previou sly shown that the neuronal isoform of nitric oxide synthase (NOS) is selectively expressed in a large fraction of trkA-expressing cholinerg ic neurons in these brain regions in the adult rat, and that NGF induc es the expression of neuronal-NOS in these cells. Herein, we show that : 1) neuronal-NOS is also localized to these neurons in the developing septum; 2) the expression of neuronal-NOS is regulated in the develop ing medial septal nucleus and vertical limb of the diagonal band; 3) n euronal-NOS regulation parallels that for other markers of basal foreb rain cholinergic neuron differentiation, such as cholineacetyltransfer ase; and 4) NGF infusion in the postnatal period induces robust increa ses in neuronal-NOS mRNA and in NOS activity in the basal forebrain. T aken together with earlier findings, our results suggest that neuronal -NOS has a role in the differentiation and mature function of septal c holinergic neurons. Through enhancing neuronal-NOS synthesis, endogeno us NGF is likely to regulate NO functions in vivo.