The physiological effects of serotonin on spontaneous and amino acid- induced activation of cerebellar nuclear cells: An in vivo study in the cat

It is well established that cerebellar efferents originate from neurons located within the cerebellar nuclei. Neurons within these nuclei receive excitatory inputs derived from the axons that arise from cells in several different regions of the brainstem and spinal cord, some of which continue on to terminate as mossy fibers and climbing fibers in the cerebellar cortex. GABA-induced inhibition in the nuclei is derived primarily from Purkinje cells located in the overlying cortex and possibly from axonal collaterals of a population of small, GABAergic nuclear neurons. In addition, a third chemically defined system of afferents that contain the monoamine serotonin forms a dense plexus of fibers throughout the cat's cerebellar nuclei. The intent of this study is to determine the physiological effects of serotonin on the spontaneous activity of cerebellar nuclear cells as well as that induced by application of the excitatory amino acids glutamate and aspartate in an adult in vivo preparation. Iontophoretic application of serotonin in anesthetized preparations suppresses both spontaneous and excitatory amino acid induced activity. In addition, interactions between serotonin and the amino acid analogs quisqualate and NMDA were analyzed; 5HT suppresses the excitatory responses of neurons to both analogs. However, there is a stronger suppressive effect on quisqualate-induced excitation as compared to that elicited by NMDA. In addition to modulating the effects of the excitatory amino acids, serotonin also potentiates the inhibitory effects of GABA. However, the effect was greatest if the neuron was initially preconditioned with GABA. In summary, serotonin acts to suppress amino acid induced activity in cerebellar nuclear neurons and to enhance GABA-mediated inhibition. The net effect is a decrease in nuclear cell activity and consequently in cerebellar output.