The striatal medium spiny neurons: what they are and how they link with Parkinson's disease

Constituting over 90% of the striatal neuronal population, medium spiny neurons (MSNs) are the projection neurons of the striatum. A distinct feature of MSNs is their rich dendritic spines, in which cortical and thalamic glutamatergic synaptic inputs are received and excite the normally silent MSNs. Another distinct feature of MSNs is their dense dopamine innervation and their high levels of dopamine (DA) D1 (D1R) and D2 (D2R) receptor expression. Equally striking is the segregation of the main DA receptors in which D1Rs are expressed in direct pathway MSNs [dMSNs] and D2Rs are expressed only in indirect pathway MSNs (iMSNs). D1R activation increases dMSN output whereas D2R activation reduces iMSN output; both of these two effects are motor-promoting. In Parkinson's disease (PD), MSNs and their D1Rs and D2Rs experience a severe lack of DA and undergo compensatory and dysregulatory changes; consequently, dMSNs and iMSNs are the key locations where abnormal neural signals for parkinsonism are initiated. The highly expressed D1Rs and D2Rs in dMSNs and iMSNs are also the primary targets of current dopaminergic anti-PD drugs.