Parkinson's Disease


Overview

Parkinson’s disease is the degradation of a specific neuron within the basal ganglia of the brain that is responsible for the planning of movement. The cluster of structures known as the basal ganglia, will send its information to the thalamus and eventually reaching the motor cortex of the brain and the said movement will result. The caudate nucleus and putamen make up the striatum structure of the basal ganglia and their neurons will receive information from the cerebral cortex, brain stem, or the thalamus. From the striatum, information will pass through the Globus pallidus, which contains both an internal and external segments. The internal segment sends information out from the basal ganglia and the external segment will play a major role in a pathway system that the basal ganglia has. The substantia nigra is divided into pars compacta and pars reticulata. Finally, the last structure is the subthalamic nuclei that will both receive input from other areas of the basal ganglia and also send information back out to different structures in the basal ganglia.
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Because the motor systems are organized in a hierarchal manner, the information that the basal ganglia receive, is processed here and then sent to the next ‘level’ of processing. There are two pathways in which the information can take and then be sent to the thalamus. Parkinson’s disease affects the pathway of information thereby producing a slow movement or no movement at all.

Basal Ganglia Pathways

Direct Pathway

The neurotransmitter, GABA, plays an important role in both the direct and indirect pathways of the basal ganglia because it typically has an inhibitory effect on its given target. When cells in the striatum are activated, they will discharge GABA onto the Globus pallidus interior (GPint). GPint also uses GABA to project to the thalamus, thereby inhibiting the activation of thalamus to the excite the motor cortex. The result of the direct pathway is an overall stimulation of the thalamus, because GABA is inhibiting the GPint, which would normally inhibit the thalamus.

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Indirect Pathway

Similar to the direct pathway, cells in the striatum will synapse with GPext with GABA. This will cause the cells in the Globus pallidus exterior (GPext) to inhibit the subthalamic nuclei. The subthalamic nuclei are then stimulated to send excitatory projections to the GPint. As we previously learned, when GPint is active, it is sending inhibitory information to the thalamus. While the result of the direct pathway it to stimulate the motor cortex, the indirect pathway works to inhibit the thalamus and thus the motor cortex will receive less information.

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Nigrostriatal Pathway

This pathway is what will regulate the balance between the direct and indirect pathway. Movement results only if there is a ‘balance’ between the two. Through the release of dopamine, the nigrostriatal pathway is able to activate or inhibit the direct or indirect pathway.

Dopamine is released within the substantia nigra pars compacta (SNc). The SNc projects into the striatum, where the activation of either pathway takes place. The direct pathway has a D1 dopamine receptor that will excite the cell and activate the direct pathway when dopamine comes in contact with this receptor. The indirect pathway has a D2 dopamine receptor that will hyperpolarize the cell when dopamine is released. This results in the inhibition of the indirect pathway, leading to more excitation within the thalamus.

Parkinson's Patients

Movement and Tremors

In patients with Parkinson's, we see a loss of dopaminergic neurons in the substantia nigra pars compacta. This will lead to an imbalance between the direct and indirect pathways. These patients will show signs of slow or no movement because the nigrostriatal pathway isn't functioning properly and the indirect pathway is more active.

This video further explains how Parkinson's manifests within people and how it effects movement.
Movement with Parkinson's

Tremors are another symptom of Parkinson's, which can also be explained by the basal ganglia. Because the balance of the direct and indirect pathways are off, there are times when dopamine may be fired in bursts and will activate movement in the hands slightly.


Quiz Questions


1. The overall result of the indirect pathway is an activation of the thalamus.
(a) True
(b) False

2. The major structure structure within the basal ganglia that is damaged in Parkinson's patients is:
(a) Subthalamic Nuclei
(b) Caudate Nucleus
(c) Substantia nigra pars compacta
(d) Substantia nigra pars reticulata

3. A common result from the release of the neurotransmitter GABA, will likely result in at the given target.

4. Basal ganglia are responsible for sending the desired movement to the thalamus.
(a) True
(b) False

5. What are the other names associated with the striatum?

References

Kandel, E. R, et al. (2013) Principles of Neural Science: Fifth Edition. New York, New York: McGraw-Hill Companies, Inc.

Knierim, J. (1997) Neuroscience Online: An Online Textbook for the Neurosciences. Retrieved from http://neuroscience.uth.tmc.edu/s3/chapter04.html .

Tutis, V. (2013) My Brain Notes for Medical Student. Electronic: Library and Archives Canada Cataloguing in Publication.

Videos and Images

https://www.youtube.com/watch?v=Be2Enu65ZE8

http://what-when-how.com/neuroscience/the-basal-ganglia-motor-systems-part-1/

http://www.shutterstock.com/pic-103879568/stock-vector-drawing-of-the-brain-showing-the-basal-ganglia-and-thalamic-nuclei.html

https://www.studyblue.com/notes/note/n/31-neuroanatomy-basal-ganglia/deck/12193171

Quiz Answers

1. B
2. C
3. Inhibition
4. B (It is involved in planning the movement)
5. Caudate and Putamen