Balance of transmitter activities in the basal ganglia loops

The basal ganglia of mammals are interconnected with the cortex in multiple loops. The main input station of the basal ganglia, the striatum, receives projections from the cortex and gives rise to two main pathways projecting back to the cortex by way of the thalamus: A direct pathway projecting to the thalamus via two GABAergic neurons and an indirect pathway that projects to the thalamus via three GABAergic neurons. Thus an excitatory cortical input to the striatum is either facilitatory (by the direct pathway) or inhibitory (by the indirect pathway) upon thalamic nuclei and on behaviour. It is speculated that by virtue of this, the basal ganglia are involved in a process of evaluation that results in suppression of ''unwanted'' and in facilitation of ''wanted'' 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 predominate over internally guided behaviours and finally akinesia occurs. A loss of dopamine results in a relative overactivity of glutamate in the striatum and in an absolute glutamatergic overactivity in the medial segment of the globus pallidus and the substantia nigra pars reticulata. Reducing the glutamatergic overactivity at these sites by local injection of glutamate receptor-antagonists or by lesions reverses akinesia and rigidity. Systemically given, NMDA receptor-antagonists, either competitive-, non-competitive- or glycine-site-antagonists, are able to reverse parkinsonian symptoms in the rat.