Serotonin Modulates Pallidal Neuronal Activity in the Awake Monkey

Serotonin (5-HT)-containing neurons in the dorsal raphe project to the external and internal segments of the pallidum, which express several 5-HT receptors. Although the involvement of 5-HT in basal ganglia movement control has been suggested, little is known about the physiological action of 5-HT in the pallidum. Previous anatomical studies and in vitro physiological studies in other brain areas have suggested the following possibilities: (1) 5-HT suppresses GABAergic inhibition through presynaptic 5-HT1B receptors; (2) 5-HT decreases the firing of pallidal neurons through postsynaptic 5-HT1A receptors; and (3) 5-HT postsynaptically excites pallidal neurons through activation of 5-HT2C, 5-HT4, or 5-HT7 receptors. To test these possibilities, we examined the effects of locally applied agonists and antagonists of 5-HT on spontaneous neuronal firing and on excitatory and inhibitory responses of pallidal neurons to electrical stimulation of the motor cortex in awake monkeys. Although in vivo experiments could not conclusively determine the receptor types or the active sites involved in the observed effects, the results suggested the following possibilities: (1) 5-HT strongly suppresses GABAergic inhibition probably through 5-HT1B receptors; (2) in the external pallidal segment, the suppression may involve additional receptors or mechanisms; and (3) 5-HT suppresses glutamatergic excitation probably through 5-HT1A (and not 5-HT1B) receptors. The present study did not isolate or identify the existence of strong, direct postsynaptic inhibitory or excitatory effects of 5-HT. Thus, present results imply that 5-HT modulates synaptic inputs of both pallidal segments and exerts a significant role in movement control.