The Basal Ganglia is a group of nuclei found in the humanbrain among other mammals. They are subcortical nuclei, gray matter, within thecerebral hemispheres. They are interconnected with the brainstem, cerebralcortex and the thalamus. The basal ganglia is part of the striatal motor system,which is responsible for conscious movement by influencing the motor systemthrough it’s interconnections with the thalamus, as well as through the motorcortex and the corticobulbar and corticospinal systems (Fix, 2007).
Parkinson’s disease is a progressivedegenerative disease belonging to a group of disorders called the motor systemdisorders. It comes about due to the death of dopamine producing cells. The mainsymptoms are tremors, starting in the hands and progressing to the rest of thebody, stiffness and rigidity, slower movement known as bradykinesia and poor balanceand coordination (Ninds.
nih.gov, 2018). It was written about in ancient textsanecdotally with no real reference to a full disorder and rather just symptomsin Egyptian papyrus and in the texts of Galen of Pergamon (Raudino, 2011), before beingwritten about in an essay by James Parkinson in 1817 (Lees, 2007). While the causeof Parkinson’s disease is unknown, it is thought to involve both genetic andenvironmental factors, as those who have a family member with Parkinson’s is morelikely to develop it in the future (Kalia and Lang, 2015).The components of the BasalGanglia are the Caudate Nucleus, Putamen, Globus pallidus, Amygdala and theClaustrum, which is located between the Putamen and the insular cortex and betweenthe external and extreme capsules of the Globus Pallidus.
The Basal Ganglia isgrouped into the Striatum, Lentiform nucleus and Corpus striatum. The striatumis composed of the caudate nucleus and the Putamen. The Lentiform nucleus iscomposed of the Putamen and the Globus pallidus. The Corpus striatum iscomposed of the Lentiform nucleus and the Caudate nucleus (Fix, 2007). All ofthe circuitry for the striatal motor system is on the same side of the brain andwires remain uncrossed. The Caudate, Putamen and Globus pallidus activate the motorthalamus, which in turn activates the motor cortex.
This pathway is importantas there is no direct pathway from the Basal Ganglia to the spinal cord (Neuroanatomy.wisc.edu,2018).
The Basal Ganglia controlsmotor control with the Striatal Motor System. The input comes in through thestriatum from other motor cortical areas, and the output signal is through theinternal membrane of the Globus pallidus. There are two pathways, the directand indirect pathways. The direct pathway is involved with upregulation ofmotor activity, and the indirect pathway downregulates it. The direct pathway,as in the name, sends signals in a direct loop. The signal from the cortexcomes in through the striatum, and is sent directly to the internal membrane ofthe Globus pallidus.
The signal uses glutamate, which is an excitatoryinhibitor. When activated by glutamate, the cortical projections from thecortex excite the neurons of the striatum. This turns on the striatal cell. Thiscell then uses an inhibitory transmitter called GABA, and the striatal axonpasses the signal to cells in the Globus pallidus internal membrane andinhibits it.
The cells from the Globus pallidus that project further to theVA/VL motor thalamus also use GABA. The Globus pallidus having more inhibitionfrom the striatum means there is less inhibition of the VA/VL cells, and so theneurons fire more. This process is known as dis-inhibition. The result is thatthis increased firing increases the firing of neurons in the motor cortex,which activates the neurons in the Lateral Corticospinal Tract (LCST) andcauses muscles to relax and contract, starting movement.
The indirect pathwayinstead starts with the striatal neurons projecting to the external membrane ofthe Globus pallidus. Cells in the external membrane project to the subthalamicnucleus, a nucleus that is just above the substantia nigra. The cells of thesubthalamic nucleus then project to the internal membrane of the Globus pallidusand continue to the direct pathway. Since the cortex, VA/VL thalamus and thesubthalamic nucleus all use the excitatory glutamate, and the striatum and bothmembranes of the Globus pallidus use GABA which is inhibitory, the signals cancelout and show that the indirect pathway is inhibitory and downregulates themotor system through the motor cortex (Neuroanatomy.wisc.edu, 2018).
The pathways can also bechanged and modulated using two neurotransmitters, dopamine and choline.Dopamine is produced in the substantia nigra, in cells called the pars compacta.Choline is produced in cholinergic neurons from within the striatum. Dopaminehas an inhibitory effect on the indirect pathway, and an excitatory effect onthe direct pathway, and so upregulates motor activity. Excitement is via the D1receptors, inhibition is by the D2 receptors.
These cholinergic neurons form a synapseon the GABAergic striatal neurons in the internal and external Globus pallidus.These, converse to dopamine, inhibit the direct pathway and excite the indirectpathway so motor activity decreases as it is downregulated. (Neuroanatomy.wisc.
edu,2018).The hallmark of Parkinson’sdisease is cell loss in the substantia nigra, affecting the ventral componentof the pars compacta. The progression of Parkinson’s disease is denoted byBraak stages 1 – 4. In Braak stages one and two, the asymptomatic stages, thereare pathological changes in the medulla oblongata, pontine tegmentum and the olfactorybulb. As it advances through Braak stages three and four, the substantia nigra,some parts of the midbrain and basal forebrain are involved, beforepathological changes happen in the neocortex near the end of the disease’progression.
These pathological signs are brought about by Lewy bodies, whichare ?-synuclein-immunoreactiveinclusions comprised of neurofilament proteins and proteins responsiblefor the break down of proteins. One protein that plays an important role is ubiquitin,which is a heat shock protein that targets other proteins for breakdown.