Serotonin in the cerebellum of the cat: An anatomical and physiological analysis

Purkinje cell activity reflects the commulative input of several cerebellar interneurons and two afferent systems. The present studies have been designed to investigate the anatomical organization and physiological actions of a third afferent system to the cerebellum. Chemically this third system of axons contains the indoleamine serotonin (5-HT). Serotoninergic axons form a fine, beaded plexus that is morphologically distinct from classically defined cerebellar afferents, climbing and mossy fibers. The distribution of serotonin immunoreactivity in the cat cerebellum was studied by using (PAP) technique. In this species, serotonion-containing axons and varicosities have an extensive and uniform distribution throughout the cerebellum however they are confined almost exclusively to the granule and Purkinje cell layers.;The brainstem origin of 5-HT projections to the cat's cerebellar cortex was studied using a double labeling technique which combines the retrograde transport of horseradish peroxidase with 5-HT immunohistochemistry. Contrary to classical views suggesting that raphe neurons are the source of 5-HT to the cerebellum, the data indicate that serotoninergic afferents arise from several reticular nuclei in the caudal brainstem. Moreover, the data indicate that there is a topographical organization in the serotoninergic projection from the medullary reticular formation to specific regions of the cat's cerebellar cortex.;In order to determine the physiological effects of serotonin in the cerebellar cortex, multibarrel electrodes were used to record the responsiveness of isolated Purkinje cells following the iontophoretic application of 5-HT. Functionally, 5-HT potently reduced the firing rate of spontaneously active Purkinje cells as well as activity induced by the application of aspartate and glutamate, the putative excitatory neurotransmitters of climbing and mossy fibers, respectively. Serotonin also potentiated the suppressive effects of GABA, and inhibitory amino acid utilized by several cerebellar interneurons. To identify which 5-HT receptor subtype(s) might be mediating the observed effects, selective receptor agonists and antagonists were used. Iontophoretic application of 8-OH-DPAT and ipsapirone, 5-HT...