Sources of p75-nerve growth factor receptor-like immunoreactivity in the rat suprachiasmatic nucleus

In mammals, the suprachiasmatic nucleus is critical for the generation of circadian rhythms and their entrainment to environmental cues. In the rat, the ventrolateral aspect of the suprachiasmatic nucleus receives a robust retinal input. This region also exhibits the most intense immunolabeling for the low-affinity nerve growth factor receptor in the forebrain. Our study was aimed at identifying the sources of this low-affinity nerve growth factor receptor immunoreactivity using immunohistochemistry combined with retrograde tract-tracing, and orbital enucleation. To determine the origin of the low-affinity nerve growth factor receptor immunoreactivity from sources extrinsic to the suprachiasmatic nucleus, unilateral injections of the retrograde tracer, Fluorogold, were made into the suprachiasmatic nucleus. Retrogradely labeled neurons that were also immunopositive for the low-affinity nerve growth factor receptor were found in both the basal forebrain and the retina. In the basal forebrain, such cells were found throughout its rostrocaudal extent, with the majority also being immunoreactive for the cholinergic marker, choline acetyltransferase. In the retina, cells retrogradely labeled with Fluorogold that were immunoreactive for low-affinity nerve growth factor receptor were located in the ganglion cell layer. Orbital enucleations were performed to confirm the findings observed following retrograde labeling in the retina. Unilateral orbital enucleations resulted in a significant reduction in low-affinity nerve growth factor receptor immunoreactivity in the contralateral suprachiasmatic nucleus compared to that seen on the ipsilateral side when examined one week post-surgery. Bilateral enucleations resulted in an equal decrease on both sides of the suprachiasmatic nucleus. Similar low-affinity nerve growth factor-like immunoreactivity was seen in the suprachiasmatic nucleus even two to four weeks after bilateral enucleations. Taken together, these findings suggest that low-affinity nerve growth factor receptors in the suprachiasmatic nucleus derive from multiple sources. While some receptors may be intrinsic to suprachiasmatic nucleus neurons, most appear to be of extrinsic origin and are located on axon terminals of basal forebrain cholinergic neurons and retinal ganglion cells.