Basal ganglia dopamine and glutamate in motor activation and plasticity

Today the basal ganglia are considered to subserve more than purely motor programming; the basal ganglia seem to be involved in procedural- and incentive learning and even in decision making according to internal representations and goals. Thus, basal ganglia even have cognitive functions. New insights into the functional anatomy support this view, or are at least in accordance with it. Two main pathways for information flow have been identified one with facilitatory, the other with inhibitory influence on behaviour. By way of this dual influence, the basal ganglia are supposed to be able to facilitate "wanted" and to inhibit "unwanted" behaviour. This hypothesis has some attractive features since it explains several so far puzzling findings. Dopamine as a modulator of the main basal ganglia loops seems to play a crucial role in deciding what is wanted or what is unwanted. Here it is speculated that every behaviour that has been performed in a certain context, is followed by a phasic dopamine signal which indicates how good (a high signal) or how bad (a poor signal) the outcome of a context-behaviour connection was. If dopamine-activity is experimentally reduced before elicitation of a specific behavioural response, this specific response will decline in an extinction like fashion. Experimentally enhanced dopamine-activity results in sensitization (i.e. in a progressively enhanced behavioural response and in a dopamine release in the striatum-accumbens complex). Further enhancement of dopamine-activity results in stereotypy which is characterized by extremely facilitated execution of a short motor response. Glutamate. The inputs to the basal ganglia are glutamatergic and originate in the cortex and in the thalamus. The major part of glutamatergic afferents project to the striatum, but also the other basal ganglia nuclei receive cortical glutamatergic inputs. A dopamine deficit, as in Parkinson's disease, results in a transmitter imbalance characterized by a glutamatergic hyperactivity in the striatum as well as in the subthalamic nucleus, the substantia nigra pars reticulata and the medial segment of the globus pallidus. Glutamate/NMDA receptor-antagonists, infused either directly into the striatum or given systemically, are able to counteract parkinsonian symptoms in rats. AMPA receptor-antagonists were ineffective in this respect. In several animal models as well as in some clinical studies with parkinsonian patients, NMDA receptor-antagonists have shown beneficial effects as adjuncts to the L-DOPA treatment: NMDA receptor-antagonists were able to enhance L-DOPA effects and to counteract tolerance after prolonged treatment with L-DOPA as well as several side-effects including dykinesias.