Striatal and extrastriatal dopamine in the basal ganglia: An overview of its anatomical organization in normal and Parkinsonian brains

Abstract

Degeneration of the nigrostriatal dopaminergic system is the characteristic neuropathological feature of Parkinson's disease and therapy is primarily based on a dopamine replacement strategy. Dopamine has long been recognized to be a key neuromodulator of basal ganglia function, essential for normal motor activity. The recent years have witnessed significant advances in our knowledge of dopamine function in the basal ganglia. Although the striatum remains the main functional target of dopamine, it is now appreciated that there is dopaminergic innervation of the pallidum, subthalamic nucleus, and substantia nigra. A new dopaminergic- thalamic system has also been uncovered, setting the stage for a direct dopamine action on thalamocortical activity. The differential distribution of D1 and D2 receptors on neurons in the direct and indirect striato-pallidal pathways has been re-emphasized, and cholinergic interneurons are recognized as an intermediary mediator of dopamine-mediated communication between the two pathways. The importance and specificity of dopamine in regulating morphological changes in striatal projection neurons provides further evidence for the complex and multifarious mechanisms through which dopamine mediates its functional effects in the basal ganglia. In this review, the role of basal ganglia dopamine and its functional relevance in normal and pathological conditions will be discussed.

Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels

“…To demonstrate the in vivo effect of ghrelin, we utilized the catalepsy model induced by a specific D2 receptor antagonist haloperidol, which has been proven to represent a reliable model for PD and is selectively reversed by clinically effective antiparkinson drugs 45 . Based on the current understanding of neural framework in basal ganglia, degeneration of nigral dopaminergic neurons leads to dopamine depletion in the striatum, resulting in an imbalance of direct and indirect pathway and subsequent motor disorders [46][47][48] . Unilateral microinjection of ghrelin causes the contralateral posturing and anticatalepsy effect, which is likely resulted from enhanced dopamine release induced by ghrelin directly and further activates the pathway of basal ganglia from the ipsilateral cortex.…”

The basal ganglia in Parkinson's disease: Current concepts and unexplained observations

“…84,86 Local interruption of dopamine terminals directed to the STN increase its activity, indicating a direct modulatory effect of dopamine on the STN. 84 We have postulated that early denervation of the STN in PD may act as a compensatory mechanism that maintains the basal ganglia output within normal limits despite a progressive loss of striatal dopamine, 87 thus potentially explaining why clinical features do not emerge until there is a 70 to 80% reduction in striatal dopamine levels.…”

DBS-implanted Parkinson's Disease Patients Show Better Olfaction Than Those Treated Medically

“…Changes in metabolism in the striatum and thalamus in PD is complex and involves alterations in receptor availability as well as neurotransmitter processing. 11 Studies in rats with 6-hydroxydopamine lesioning have shown a number of changes in metabolism with prolonged high frequency stimulation (HFS), including normalization of COX levels in the substantia nigra with HFS. 12 In the same model, Cytochrome oxidase I mRNA levels in cortical regions have also shown to normalize following HFS.…”