The cortex and between the external and extreme

The Basal Ganglia is a group of nuclei found in the human
brain among other mammals. They are subcortical nuclei, gray matter, within the
cerebral hemispheres. They are interconnected with the brainstem, cerebral
cortex and the thalamus. The basal ganglia is part of the striatal motor system,
which is responsible for conscious movement by influencing the motor system
through it’s interconnections with the thalamus, as well as through the motor
cortex and the corticobulbar and corticospinal systems (Fix, 2007). Parkinson’s disease is a progressive
degenerative disease belonging to a group of disorders called the motor system
disorders. It comes about due to the death of dopamine producing cells. The main
symptoms are tremors, starting in the hands and progressing to the rest of the
body, stiffness and rigidity, slower movement known as bradykinesia and poor balance
and coordination (Ninds.nih.gov, 2018). It was written about in ancient texts
anecdotally with no real reference to a full disorder and rather just symptoms
in Egyptian papyrus and in the texts of Galen of Pergamon (Raudino, 2011), before being
written about in an essay by James Parkinson in 1817 (Lees, 2007). While the cause
of Parkinson’s disease is unknown, it is thought to involve both genetic and
environmental factors, as those who have a family member with Parkinson’s is more
likely to develop it in the future (Kalia and Lang, 2015).

The components of the Basal
Ganglia are the Caudate Nucleus, Putamen, Globus pallidus, Amygdala and the
Claustrum, which is located between the Putamen and the insular cortex and between
the external and extreme capsules of the Globus Pallidus. The Basal Ganglia is
grouped into the Striatum, Lentiform nucleus and Corpus striatum. The striatum
is composed of the caudate nucleus and the Putamen. The Lentiform nucleus is
composed of the Putamen and the Globus pallidus. The Corpus striatum is
composed of the Lentiform nucleus and the Caudate nucleus (Fix, 2007). All of
the circuitry for the striatal motor system is on the same side of the brain and
wires remain uncrossed. The Caudate, Putamen and Globus pallidus activate the motor
thalamus, which in turn activates the motor cortex. This pathway is important
as there is no direct pathway from the Basal Ganglia to the spinal cord (Neuroanatomy.wisc.edu,
2018).

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The Basal Ganglia controls
motor control with the Striatal Motor System. The input comes in through the
striatum from other motor cortical areas, and the output signal is through the
internal membrane of the Globus pallidus. There are two pathways, the direct
and indirect pathways. The direct pathway is involved with upregulation of
motor activity, and the indirect pathway downregulates it. The direct pathway,
as in the name, sends signals in a direct loop. The signal from the cortex
comes in through the striatum, and is sent directly to the internal membrane of
the Globus pallidus. The signal uses glutamate, which is an excitatory
inhibitor. When activated by glutamate, the cortical projections from the
cortex excite the neurons of the striatum. This turns on the striatal cell. This
cell then uses an inhibitory transmitter called GABA, and the striatal axon
passes the signal to cells in the Globus pallidus internal membrane and
inhibits it. The cells from the Globus pallidus that project further to the
VA/VL motor thalamus also use GABA. The Globus pallidus having more inhibition
from the striatum means there is less inhibition of the VA/VL cells, and so the
neurons fire more. This process is known as dis-inhibition. The result is that
this increased firing increases the firing of neurons in the motor cortex,
which activates the neurons in the Lateral Corticospinal Tract (LCST) and
causes muscles to relax and contract, starting movement. The indirect pathway
instead starts with the striatal neurons projecting to the external membrane of
the Globus pallidus. Cells in the external membrane project to the subthalamic
nucleus, a nucleus that is just above the substantia nigra. The cells of the
subthalamic nucleus then project to the internal membrane of the Globus pallidus
and continue to the direct pathway. Since the cortex, VA/VL thalamus and the
subthalamic nucleus all use the excitatory glutamate, and the striatum and both
membranes of the Globus pallidus use GABA which is inhibitory, the signals cancel
out and show that the indirect pathway is inhibitory and downregulates the
motor system through the motor cortex (Neuroanatomy.wisc.edu, 2018).

The pathways can also be
changed 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. Dopamine
has an inhibitory effect on the indirect pathway, and an excitatory effect on
the direct pathway, and so upregulates motor activity. Excitement is via the D1
receptors, inhibition is by the D2 receptors. These cholinergic neurons form a synapse
on the GABAergic striatal neurons in the internal and external Globus pallidus.
These, converse to dopamine, inhibit the direct pathway and excite the indirect
pathway so motor activity decreases as it is downregulated. (Neuroanatomy.wisc.edu,
2018).

The hallmark of Parkinson’s
disease is cell loss in the substantia nigra, affecting the ventral component
of the pars compacta. The progression of Parkinson’s disease is denoted by
Braak stages 1 – 4. In Braak stages one and two, the asymptomatic stages, there
are pathological changes in the medulla oblongata, pontine tegmentum and the olfactory
bulb. As it advances through Braak stages three and four, the substantia nigra,
some parts of the midbrain and basal forebrain are involved, before
pathological changes happen in the neocortex near the end of the disease’
progression. These pathological signs are brought about by Lewy bodies, which
are ?-synuclein-immunoreactive
inclusions comprised of neurofilament proteins and proteins responsible
for 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.

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