BALANCE OF TRANSMITTER ACTIVITIES IN THE BASAL GANGLIA LOOPS

The basal ganglia of mammals are interconnected with the cortex in mul tiple loops. The main input station of the basal ganglia, the striatum , receives projections from the cortex and gives rise to two main path ways projecting back to the cortex by way of the thalamus: A direct pa thway projecting to the thalamus via two GABAergic neurons and an indi rect pathway that projects to the thalamus via three GABAergic neurons . Thus an excitatory cortical input to the striatum is either facilita tory (by the direct pathway) or inhibitory (by the indirect pathway) u pon thalamic nuclei and on behaviour. It is speculated that by virtue of this, the basal ganglia are involved in a process of evaluation tha t results in suppression of ''unwanted'' and in facilitation of ''want ed'' behaviour. With decreasing dopamine activity in the striatum and in turn increasing inhibition of the thalamus, arbitrary switching of behaviours is suppressed, then externally guided behaviours predominat e over internally guided behaviours and finally akinesia occurs. A los s of dopamine results in a relative overactivity of glutamate in the s triatum and in an absolute glutamatergic overactivity in the medial se gment of the globus pallidus and the substantia nigra pars reticulata. Reducing the glutamatergic overactivity at these sites by local injec tion of glutamate receptor-antagonists or by lesions reverses akinesia and rigidity. Systemically given, NMDA receptor-antagonists, either c ompetitive-, non-competitive- or glycine-site-antagonists, are able to reverse parkinsonian symptoms in the rat.