So Parkinson's disease leads to the loss of dopaminergic neurons. I understand how the direct pathway (an excitatory pathway) is inhibited, leading to a loss of movement. However, how can the loss of dopamine neurons cause enhancement of the indirect pathway (which enhances its inhibitory effect, leading to a loss of movement)?

I assumed that loss of neurons would decrease stimulation of both pathways.

  • $\begingroup$ It's not that simple. There are still several theories out there...each of them fairly complex. $\endgroup$ – Memming Feb 6 '17 at 1:25

The dopaminergic neurons of the substantia nigra pars compacta are a part of neither the direct nor the indirect pathway. The dopaminergic system rather acts as a modulator between those two pathways. More dopamine steers the system towards the direct pathway, less dopamine towards the indirect pathway.

One of the best explanations of the basal ganglia that I've ever seen were video lectures by Dr. Najeeb on youtube.

explanation of the basal ganglia pathways

pathologies involving the basal ganglia

At the beginning of the second video there is a short review of the pathways he explains in the first one. At 5:06 he starts talking about Parkinson's disease.

A paper about the topic:

Functional organization of the basal ganglia: Therapeutic implications for Parkinson's disease (Obeso et al. (2008)

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