Download 1.In the direct pathway

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Basal ganglia
The basal ganglia, like the cerebellum, constitute another accessory
motor system that functions usually not by itself but in close association
with the cerebral cortex and corticospinal motor control system. In fact,
the basal ganglia receive most of their input signals from the cerebral
cortex itself and also return almost all their output signals back to the
cortex. The basal ganglia include:
 caudate nucleus,
 putamen
(Together the caudate and putamen are called the striatum.),
 globus pallidus, which include internal globus pallidus (internal
GP) and external globus pallidus (external GP)
 There also are associated nuclei, including the subthalamic
nucleus of the diencephalon, and the substantia nigra of the
midbrain. They are located mainly lateral to and surrounding the
thalamus, occupying a large portion of the interior regions of both
cerebral hemispheres.
Figure: The basal ganglia.
Neuronal Circuitry of the Basal Ganglia.
All cortical areas involved in the planning and execution of movements
project to the striatum (caudate and putamen). Striatal neurons
receiving these cortical inputs then project to the globus pallidus, which
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in turn projects to the thalamus. fiber from thalamus in turn projects to
motor cortex. So, the caudate, putamen and globus pallidus act on the
motor thalamus, which acts on the motor cortex. There are no
descending pathways that go from the basal ganglia directly to the spinal
cord. There are two important pathways through which striatal
information reaches (internal GP) - the direct pathway and the indirect
pathway. These two pathways have opposite effects on motor activity:
1.In the direct pathway, the circuit begin mainly in the motor cortex,
from here fibers pass to striatum then to the internal portion of the
globus pallidus, next to the thalamus, and finally return to the motor
cortex.
Neurotransmitter of direct pathway
The motor cortex send excitatory fibers (glutamate secreting neuron) to
striatal cells, the striatal cells project directly to (internal GP). The striatal
fiber that project to internal GP uses the inhibitory transmitter GABA.
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The cells in (internal GP) project to thalamus these fibers are also use
GABA (inhibitory transmitter). The consequence of this pathway is more
inhibition of GP (internal) which lead to less inhibition (disinhibition) of
motor thalamus (disinhibition), the net result is increase the excitatory
drive from thalamus to cortex.
REMEMBER, THE DIRECT PATHWAY TURNS UP MOTOR ACTIVITY.
2. In indirect Pathway, the circuit begin mainly in the motor cortex, from
here fibers pass to striatum then to the external portion of the globus
pallidus (external GP). from external GP fibers projects to the
subthalamic nucleus. Cells in the subthalamic nucleus then project to
GP(internal), which in turn projects to the thalamus.
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Neurotransmitter of indirect pathway
A key thing to remember is that the projection neurons in cortex,
subthalamic nucleus and thalamus use glutamate; their effects are
excitatory. The projection neurons in striatum and both segments of
globus pallidus use GABA; their effects are inhibitory. So, applying the
pluses (excitation) and minuses (inhibition) in the indirect pathway
reveals that the consequence of the indirect pathway is to decrease the
excitatory drive from thalamus to cortex.
The Indirect Pathway turns DOWN the motor thalamus and, in turn,
motor cortex. Thus, it TURNS DOWN motor activity.
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Function of the Basal Ganglia in
1. One of the principal roles of the basal ganglia in motor control is to
function in association with the corticospinal system to control complex
patterns of motor activity. An example is the writing of letters, cutting
paper with scissors, hammering nails, shooting a basketball through a
hoop, passing a football, throwing a baseball, most aspects of
vocalization, controlled movements of the eyes .
2. Cognitive Control of motor activity, using both sensory input to the
brain plus information already stored in memory. A good example of this
would be a person seeing a lion approach and then responding
instantaneously and automatically by
(1) turning away from the lion,
(2) beginning to run.
(3) even attempting to climb a tree.
Without the cognitive functions, the person might not have the
instinctive knowledge, without thinking for too long a time, to respond
quickly and appropriately. Thus, cognitive control of motor activity
determines subconsciously, and within seconds, which patterns of
movement will be used together to achieve a complex goal that might
itself last for many seconds.
3.Function of the Basal Ganglia to Change the Timing and to Scale the
Intensity of Movements
Two important capabilities of the brain in controlling movement are
(1) to determine how rapidly the movement is to be performed
(2) to control how large the movement will be.
For instance, a person may write the letter “a” slowly or rapidly. Also, he
or she may write a small “a” on a piece of paper or a large “a” on a
chalkboard. Regardless of the choice, the proportional characteristics of
the letter remain nearly the same.
DOPAMINERGIC and CHOLINERGIC Modulation of Direct and Indirect
Pathways
Striatal neurons are modulated by two important neuromodulatory
systems. Each of these systems differentially affects the direct and
indirect pathways, thereby altering their balance and the amount of
motor activity that is produced.
1.the substantia nigra, send Dopamine secreting neuron into the
striatum. Dopamine has an excitatory effect upon cells in the striatum
that are part of the Direct Pathway. This is via D1 receptors. Dopamine
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has an inhibitory effect upon striatal cells associated with the Indirect
Pathway. This is via D2 receptors. In other words, the direct pathway
(which turns up motor activity) is excited by dopamine while the indirect
pathway (which turns down motor activity) is inhibited. Both of these
effects lead to increased motor activity.
2. There is a population of cholinergic (ACh) neurons in the striatum
whose axons do not leave the striatum (called interneurons or local
circuit neurons). These cholinergic interneurons synapse on the
GABAergic striatal neurons that project to GP(internal) and on the
striatal neurons that project to GP(external). The cholinergic actions
INHIBIT striatal cells of the Direct pathway and EXCITE striatal cells of the
Indirect pathway. Thus ACh inhibits the direct and excites the indirect
pathway, the effect of the cholinergic striatal interneurons is to decrease
motor activity. ACh TURNS DOWN MOTOR ACTIVITY
Parkinson’s disease(paralysis agitans),
Parkinson’s disease, results from widespread destruction of that portion
of the substantia nigra (the pars compacta) that sends dopaminesecreting nerve fibers to the caudate nucleus and putamen. The disease
is characterized by
(1) rigidity of much of the musculature of the body,
(2) involuntary tremor of the involved areas even when the person is
resting at a fixed rate of 3 to 6 cycles per second, and
(3) serious difficulty in initiating movement, called akinesia.
Treatment with l-Dopa. Administration of the drug Ldopa to patients
with Parkinson’s disease usually ameliorates many of the symptoms,
especially the rigidity and akinesia. The reason for this is believed to be
that L-dopa is converted in the brain into dopamine, and the dopamine
then restores the normal balance between inhibition and excitation in
the caudate nucleus and putamen.
Huntington’s Disease (Huntington’s Chorea)
Huntington’s disease is a fatal autosomal dominant disorder in which
patients present with an insidious onset of chorea (quick random
involuntary movements, often of the extremities), progressive dementia,
and behavioral disorders. The key pathologic lesion that characterizes
this condition is severe idiopathic degeneration of GABA neurons in the
striatum, resulting in atrophy of the caudate nucleus.
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