The development of the serotonergic fiber network of the lateral ventricles of the rat brain: a light and electron microscopic immunocytochemical analysis.

The development of the serotonergic innervation of the lateral ventricles of the rat brain during the first five postnatal weeks was studied with immunocytochemical techniques at the light and electron microscopic levels. In the lateral ventricles of newborn rats serotonergic fibers are only rarely seen. During the first postnatal week the number of serotonergic fibers increases but they are straight and thick, bearing only a few varicosities. By the end of the second postnatal week, however, they become finer, exhibit a large number of varicosities, and form a dense supraependymal network. During the following weeks this network becomes slightly denser but the morphology of fibers as well as their distribution pattern remain unchanged. Examination of sagittal vibratome sections revealed that a group of serotonergic fibers leaves the medial forebrain bundle and turning dorsocaudally between the corpus callosum and the caudate/putamen enter the lateral ventricle from its rostral pole. They then spread to form the supraependymal network of the lateral ventricles and probably of the rest of the ventricular system. Ultrastructural analysis showed that serotonin varicosities are located close to the ventricular surface of the ependymal lining but never make synapses with the ependymal cells. Examination of a large number of labeled fibers and varicosities showed that they are never located between the ependymal cells or in the subependymal layer. This finding was confirmed by examining series of semithin sections. On the basis of these and previous findings we suggest that serotonergic fibers arising in the midbrain raphe nuclei enter the lateral ventricle from its rostral pole, form a dense network within the ventricles, and release their content into the cerebrospinal fluid. This system, as judged with morphological criteria, matures by the end of the second postnatal week.