Modulation of dorsal spinocerebellar responses to limb movement. I. Effect of serotonin

Spinocerebellar neurons (DSCT) receive converging sensory information from various sensory receptors in the hindlimbs and lower trunk. Previous studies have shown that sensory processing by DSCT neurons results in a representation of global hindlimb kinematic parameters such as the length and the orientation of the limb axis. In addition to the sensory input, the DSCT circuitry also receives a descending input from the raphe nuclei in the brain stem. Recent studies have demonstrated that the raphe serotonergic terminals synapse directly on DSCT neurons and exert a differential modulatory influence on their sensory inputs. We examined the role of serotonergic modulation on the DSCT representation of hindlimb kinematic parameters by recording DSCT activity during passive hindlimb movements before and after perturbing serotonergic transmission. We used two types of perturbation: electrical stimulation of the raphe areas in the brain stem to release serotonin in the spinal cord (42 neurons) and intravenous administration of serotonergic agonists or antagonists, mostly the 5HTP2 antagonist ketanserin (30 neurons). We found that movement responses were altered in approximately 70% of the DSCT units studied with each protocol. Changes could include shifts in mean firing rate, increases or decreases in response amplitude, and changes in response waveform. We used a principal component analysis (PCA) to examine waveform components and to determine how they contributed to the response waveform changes caused by serotonin perturbation. Such changes could be explained by new or different response components that might indicate a modification in the data processing or by a different weighting of existing components that might indicate a modification of synaptic weighting. The results were consistent with the second alternative. We found that the same underlying response components could account for both control responses and those altered by serotonin perturbations. The observed changes in waveform could be entirely accounted for by a re-weighting of response components. In particular, the changes observed after raphe stimulation could be accounted for by selective changes in the weighting of the first principal component (PC) with only minor changes of the weighting of the second PC. Because these response components were shown previously to correlate with the limb axis orientation and length trajectories respectively, the finding is consistent with the idea that limb axis length and orientation information are processed separately within the spinal circuitry.