In Parkinsons disorder the substanstia nigra pars compacta get affected and there is destruction of the dopaminergic neurons, which ultimately disturbs the direct and indirect pathways. Now we know indirect pathway is overall inhibitory to movement and direct pathway is overall stimulatory. Now because both of these pathways are not working properly, can we consider this as a reason for both hypokinetic and hyperkinetic disorders seen in Parkinsons? Or there is some other explanation.


2 Answers 2


I am not highly proficient in neuroscience, but I managed to find the following from Sonne et al. (2020) which may help while you wait for a more proficient answer. (Emphasis mine)

While most forms of Parkinson disease are due to the insidious degeneration of the substantia nigra over a lifetime or during old age, the cause of that degeneration is unknown. These forms of Parkinson disease are termed idiopathic due to their unknown cause. A great deal of research is being done to identify these causes, which can include peripheral inflammation,[15] metabolic insufficiency,[16] and various environmental toxins,[17][18][19] which have been shown to affect the substantia nigra. Several other neurological conditions exhibit parkinsonian-like signs and symptoms by affecting the dopaminergic neurons of the substantia nigra. These include drug-induced parkinsonism in which a patient is taking a pharmaceutical compound, such as antipsychotics and antihypertensive, that affects dopamine metabolism.

  1. Brydon L, Harrison NA, Walker C, Steptoe A, Critchley HD. Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiatry. 2008 Jun 01;63(11):1022-9. [PMC free article] [PubMed]
  2. Yang L, Wang H, Liu L, Xie A. The Role of Insulin/IGF-1/PI3K/Akt/GSK3β Signaling in Parkinson's Disease Dementia. Front Neurosci. 2018;12:73. [PMC free article] [PubMed]
  3. Langston JW, Irwin I, Langston EB, Forno LS. 1-Methyl-4-phenylpyridinium ion (MPP+): identification of a metabolite of MPTP, a toxin selective to the substantia nigra. Neurosci Lett. 1984 Jul 13;48(1):87-92. [PubMed]
  4. Gash DM, Rutland K, Hudson NL, Sullivan PG, Bing G, Cass WA, Pandya JD, Liu M, Choi DY, Hunter RL, Gerhardt GA, Smith CD, Slevin JT, Prince TS. Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity. Ann Neurol. 2008 Feb;63(2):184-92. [PubMed]
  5. Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW. Rotenone, paraquat, and Parkinson's disease. Environ Health Perspect. 2011 Jun;119(6):866-72. PMC free article PubMed


Sonne J, Reddy V, Beato MR. (2020) Neuroanatomy, Substantia Nigra. In: StatPearls. Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536995/


The motor system has a LOT of paralell pathways. The model you state is very old and told in med school because it looks nice, but it just doesn't fit the reality. For example, there are a lot of papers trying to come up with models of tremor generation involving corticothalamic loops and beyond.

I suggest reading Motor Control chapters of this book, which is very short and introductory, but beautiful. Neurophysiology: A Conceptual Approach by R. Carpenter, fifht edition. Or you could go with Gazzaniga and even better Kandels'.

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    $\begingroup$ "The model you state is very old and told in med school because it looks nice, but it just doesn't fit the reality." I have a problem with this as I cannot understand why they would teach this in med school if it doesn't fit reality. Can you cite some reputable sources to back this up? $\endgroup$ Feb 28, 2021 at 17:01
  • $\begingroup$ Welcome to Medical Sciences. Chris is right to ask for supporting references. We work differently than most SE sites in that we have a strict policy that all answers should be backed up with reliable references so the answer can be independently verified. You don't have to write a doctoral thesis, just enough to back up your assertions of fact. Unreferenced claims can lead to answers being deleted. $\endgroup$ Mar 1, 2021 at 0:42

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