INVOLVEMENT OF BASAL GANGLIA TRANSMITTER SYSTEMS IN MOVEMENT INITIATION

The basal ganglia have been implicated in a number of important motor functions, in particular in the initiation of motor responses. Accordi ng to the current model of basal ganglia functions, motor initiation i s supposed to be associated with an inhibition of basal ganglia output structures (substantia nigra pars reticulata/entopeduncular nucleus) which, in turn. might be brought about by corresponding striatal activ ity changes conveyed via direct and indirect intrinsic pathways to the substantia nigra pars reticulata and the entopeduncular nucleus. Rode nt studies using neuropharmacological manipulations of basal ganglia t ransmitter systems by neurotoxins or drugs provide converging evidence that dopamine within the caudate-putamen, but also within extrastriat al basal ganglia nuclei, is involved in motor initiation by modulating the activity of direct and indirect intrinsic pathways. However, the striatal segregation of dopamine D-1 and D2 receptors in control of th e direct and indirect projection neurons seems not to be maintained th roughout the basal ganglia. In dopamine intact animals, striatal gluta mate plays a major role in response initiation probably through action s on striatopallidal neurons involving N-methyl-D-aspartate, but not l pha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor s. Striatal adenosine might also contribute to movement initiation by acting on adenosine A(2A) receptors located on striatopallidal neurons . Analysis of two integral parts of the indirect pathway revealed that inactivation of the subthalamic nucleus was found to facilitate respo nse initiation, while inactivation of the globus pallidus resulted in facilitation as well as inhibition of response initiation indicating a complex contribution of this latter nucleus. Glutamate and gamma-amin o-butyric acid (GABA) controlling the activity of the substantia nigra pars reticulata could be involved in control of response initiation i n a way predicted by the simplified model of basal ganglia functions. In contrast, the role of the entopeduncular nucleus in response initia tion and its control through GABA and glutamate is at variance with th is hypothesis, suggesting functional differences of the output structu res. Taken together, neurochemical systems of the basal ganglia signif icantly contribute to intact response initiation by mechanisms which a re only partly consistent with predictions of the current functional s cheme of the basal ganglia. This suggests that a more complex model is required to account for these disparate findings. (C) 1998 Elsevier S cience Ltd. All rights reserved.