# Introduction to Parkinson's Science/Q Page 3

The characteristic symptoms of Parkinson's arise because there is a deficit in the production of the neurotransmitter, dopamine, in a particular part of the brain.

## How exactly are the basal ganglia circuits affected by the lack of dopamine?

If the reader is not familiar with the structure of nerve cells (neurons) and how signals are passed from one to another then the wikipedia pages neuron and neurotransmitter could be of help.
Figs 1 and 2 illustrate the basic structures and transmission mechanisms:
| Fig 1. The axons of neurons in the substantia nigra have proportionately much longer axons than in this diagram because they have to project a long way to reach the striatum | Fig 2. The axonal terminals of neurons communicate with the dendrites of the receiving neurons by the passage of neurotransmitters across the synapse |
Fig 3 shows where the basal ganglia lie within the brain. The arrows in the lower part of the diagram show the paths the nerve fibres (bundles of axons) take between the ganglia to deliver the various neurotransmitters to their targets.
Diagrams like Figs 4 & 5 below are usually used to illustrate the main nuclei in the basal ganglia and to explain how Parkinson's motor symptoms arise when cells in the substantia nigra are lost and dopamine production is impaired.
* Fig 4. The left hand side shows the normal brain and the right hand side shows the changed levels of neurotransmitters in the Parkinsonian brain. Excitatory pathways are shown as blue and inhibitory pathways as red
* Fig 5. Connectivity diagram showing excitatory
* glutamatergic pathways as red, inhibitory GABAergic pathways as blue, and modulatory dopaminergic pathways as magenta. (Abbreviations: GPe: globus pallidus external; GPi: globus pallidus internal; STN: subthalamic nucleus; SNc: substantia nigra compacta; SNr: substantia nigra reticulata)
(Note that the colours for the inhibitory and excitatory signals are reversed between the two diagrams.)
A full explanation is given in wikipedia: Basal ganglia - Circuit connections. The essence of the explanation is that from the cortex to the thalamus there are two pathways through the basal ganglia before the signals return to the cortex for sending to the muscles. These are termed the direct and indirect pathways. You can trace these on the diagrams. In Fig 3 the direct pathway goes through the Green + on the blue arrow and the indirect pathway goes through the red - on the blue arrow. In Fig 4 the direct pathway goes through D1 in the Putamen and the indirect pathway goes through D2.
The signals going along the direct pathway have the effect of exciting the output from the thalamus to stimulate action whereas those going along the indirect pathway have the effect of suppressing action. The signals transmitted by dopamine from the substantia nigra pars compactor affect the balance between the two pathways.
In the Parkinsonian brain, the balance between the pathways is disturbed and the result is that the inhibitory output predominates and stiffness in the target muscles and slowness of movement is experienced.
This usual explanation is based on supposed changes in relative firing rates of neurons in the basal ganglia circuits whereas recent work suggests that oscillatory states within and between the nuclei promoted by dopamine depletion are a more important factor.
Replacing dopamine or compensating for its loss is the basis for much of the current therapy for Parkinson's and is explained in the subpage What are the current therapies for Parkinson's?
* ↑ Weinberger, Moran, and Jonathan O Dostrovsky. “A Basis for the Pathological Oscillations in Basal Ganglia: The Crucial Role of Dopamine.” Neuroreport 22, no. 4 (March 9, 2011): 151–156, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076312/.
* Follow-up questions
* What other PD symptoms are there?
* Other symptoms of Parkinson’s especially non-motor symptoms: bladder and bowel, olfaction, speech and swallowing, depression, dementia. The origin of the non-motor symptoms
* The origins of these other symptoms
* The life cycle and stages of Parkinson’s including the evidence for it beginning outside of the brain.
* What are the current therapies for Parkinson's?
* Dopamine replacement therapies, surgery and other non-drug therapies
* Third follow-up question -- ?
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