Basal+Ganglia+II

=The Basal Ganglia = by Daniel Adam

=Outline:=

The basal ganglia are a series of four nuclei that is responsible for regulating motor function. It is constructed of the corpus striatum, globus pallidus, substantia nigra, and subthalamic nuclei. These nuclei form two distinct tracts that either induce movement or suppress movement and is an essential circuit for motor control. These pathways are controlled by three neurotransmitters. The basal ganglia are directly connected to motor areas responsible for head and eye movement. Dysfunction affecting the basal ganglia causes the complete halt of motion as in Parkinson’s disease. It also can cause uncontrolled motion in the case of Huntington’s disease.

=Functional Anatomy:=

The basal ganglia are subcortical nuclei that are located in the telencephalon, diencephalon, and midbrain. In primates, the putamen and the caudate form the major input structure known as the corpus striatum. In lower mammalian brains, the corpus striatum is just one set of nuclei instead of both the putamen and the caudate. The corpus striatum is separated into its two parts by the internal capsule, which are nerves separating the thalamus and cerebral cortex. The caudate is a large C shaped nucleus that is connected to the putamen by grey matter bridges that pass through the internal capsule. The corpus striatum has direct neuronal connections to the other nuclei in the basal ganglia. It is a GABA-ergic nucleus that has direct control over the globus pallidus, and the substantia nigra pars reticulata.

The globus pallidus sits inferior and medial to the corpus striatum. This nucleus is divided into two nuclei: the globus pallidus pars externa, and the globus pallidus pars interna. These are both GABA-ergic nuclei. The globus pallidus pars externa innervates the subthalamic and the globus pallidus pars interna innervates the thalamus.

The substantia nigra is divided into the substantia nigra pars reticulate and the substantia nigra pars compacta. These nuclei are located inferior to the subthalamic nuclei. The substantia nigra pars compacta is superior to the substantia nigra pars reticulata. The substantia nigra pars compacta is the only dopaminergic in the basal ganglia and both excites and inhibits different pathways in the basal ganglia by innervating the corpus striatum. The substantia nigra pars reticulata is GABA-ergic and innervates the thalamus.

The final nucleus is the subthalamic nuclei. It is located inferior to the internal capsule and superior to the substantia nigra. It is a glutamatergic and innervates the globus pallidus pars interna and the substantia nigra pars reticulata.

=Basal Ganglia’s Input and Output:=

The Basal ganglia is a circulatory circuit with the neocortex connected through the thalamus. There are multiple projections from the cortex returning to the primary motor cortex. The three major neurotransmitters that innervate the basal ganglion are γ-aminobutyric acid (GABA), glutamic acid, and dopamine. γ-Aminobutyric acid has an inhibitory effect on the nuclei. In contrast glutamic acid is an amino acid that has an excitatory effect. Dopamine has the ability to excite and inhibit different pathways in the basal ganglia.

Input:
The cortex is the main input to the basal ganglia. The neurotransmitter involved is glutamic acid which has an excitatory effect on the corpus striatum. The basal ganglion receives both sensory and motor input. The sensory information projects from the cortex to the putamen of the basal ganglia. The sensory information comes from the primary somatosensory cortex and the secondary somatosensory cortex. The putamen also receives visual information from the visual cortices, auditory input from the auditory association areas, motor information from the prefrontal cortex, and some information from the supplementary motor and the primary motor cortices.

The caudate receives mostly motor input that deals with eye movement. This motor stimuli projects from the primary motor cortex, the supplementary motor cortex, frontal eye fields, and prefrontal cortex.

Postmortem evaluation of the corpus striatum revealed patches of lighter dense staining area surrounded by densely staining areas. This was done using acetylcholinesterase, an enzyme that reacts with acetylcholine, a neurotransmitter. These patches are called striosomes, and the surrounding is called the matrix. These areas were discovered to receive and project different information. The striosomes receive innervation from and project to the mainly substantia nigra pars reticulata. The matrix is much larger and receives information from the rest of the cortex, and projects to both output nuclei.

Output:
The striatum projects to the output nuclei which are the substantia nigra pars reticulata and the globus pallidus pars interna, and to the globus pallidus pars externa. From the output nuclei, the neurons project to the mediodorsal nuclei, ventral anterior nuclei, and the ventral lateral nuclei of the thalamus. This is a GABA-ergic connection that inhibits these nuclei to suppress movement. The thalamus then projects into the frontal lobe. The majority of the projections are to the supplementary motor cortex with some of the projection to the primary motor cortex. These two motor cortices have direct connection to the motor areas of the brain stem and the spinal cord motor areas.

The signal also projects to the superior colliculus without passing through the thalamus. The superior colliculus is part of the midbrain, and this direct innervation is to control eye movement as well as head movement through the technospinal tract. The basal ganglia also directly project to the pedunclopontine nucleus. The main role of this is to help control posture and gait.

=Pathways:=

The major motor pathway is the corticostriatal pathway. This pathway is responsible for the control of movement. It is divided into two pathways: the direct and indirect pathways. The direct pathway is responsible for allowing movementThe indirect pathway, on the other hand, suppresses movement. This means that the indirect pathway is the common pathway tosuppress sporadic and unwanted movement.

Direct pathway:
The substantia nigra pars compacta produces dopamine which excites the D1 pathway exciting the direct tract, and inhibits the D2 tract and inhibiting the indirect tract. This is to allow the motor signal to go through so the motor cortices can generate body movement because the indirect pathway is constantly suppressing movement. The corpus striatum innervates the globus pallidus pars interna and the substantia nigra pars reticulata. This involves the synaptic transmission of GABA. The globus pallidus pars interna and the substantia nigra pars reticulata then send GABA as an inhibitory signal to the mediodorsal nuclei, ventral anterior nuclei, and the ventral lateral nuclei of the thalamus. The globus pallidus pars interna and the substantia nigra pars reticulata are inhibited so the innervation of the thalamic nuclei is disinhibited. Thus the thalamus can excite the cortex and can generate movement.

Since the dopamine inhibits the indirect pathway the globus pallidus pars externa inhibits the subthalamic nuclei to prevent the excitation of the globus pallidus pars interna and the substantia nigra pars reticulata.

Indirect pathway:
Without the dopaminergic input from the substantia nigra pars compacta the information passes through the indirect pathway. From the corpus striatum innervates the globus pallidus pars externa with GABA. The globus pallidus pars externa projects to the subthalamic nuclei. This is a GABA-ergic synaptic connection. Since the globus pallidus pars externa is inhibited, this disinhibits the subthalamic nuclei. The subthalamic nuclei project to the globus pallidus pars interna and the substantia nigra pars reticulata. This is a glutamatergic synapse that excites the globus pallidus pars interna and the substantia nigra pars reticulata. The excitation of the globus pallidus pars interna and the substantia nigra pars reticulata produces GABA that inhibits the mediodorsal nuclei, ventral anterior nuclei and the ventral lateral nuclei of the thalamus. This prevents the generation of the movement.

=Dysfunctions:=

Basal Ganglia dysfunctions can be caused by genetic factors, autoimmunity, and unknown factors. The similarity is that many of them affect the ability to control movement. Patients can either experience difficultly in the production motion or the ability to suppress unwanted movement.

Parkinson’s disease:
Parkinson’s disease is a hypokinetic disorder, meaning that it causes the patient to lose motor generation. Patients experience tremors, rigidity, a shuffled gait which is a common indicator of Parkinson’s disease, and trouble extending the arms. This is believed to be caused by the production of dopamine by the substantia nigra pars compacta. This decreases the frequency of the direct pathways, and increases the frequency of the indirect pathway. The subthalamic nuclei cause an increase of GABA innervation of the globus pallidus pars interna and the substantia nigra pars reticulata. This inhibits the thalamus and does not allow for movement generation. A common treatment is L-Dopa which is broken down into dopamine by the body to allow the direct pathway to occur.

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Huntington’s disease:
In comparison to Parkinson’s disease, Huntington’s disease is a hyperkinetic disorder. Huntington’s disease is recessive genetic disorder that can affect patient as early as forty years of age. It is characterized by sporadic, jerky motion of the extremities, and facial movements. The symptoms are caused by the degeneration of the indirect pathway. The neurons innervating the globus pallidus pars externa, from the corpus striatum are lost. This causes the decreases oftheglutamatergic effect of the subthalamic nuclei on the output nuclei disinhibiting the thalamus. This allows the cortex to constantly stimulate the basal ganglia and with no indirect pathway to stop unwanted movements.

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Saccadic Eye Movement Disorders:
Saccadic eye movement disorders are commonly present in patients with both Parkinson’s disease and Huntington’s disease. These are characterized by a decrease in saccade velocities and interruptions in saccades. It is believed to be caused by a decrease in stimuli from the corpus striatum in both disorders. More recent studies have suggested that substance P, a neuropeptide is decreased in the corpus striatum’s innervation of the substantia nigra pars reticulata.

Autoimmune Basal Ganglion disorders:
These disorders are caused when the immune system recognizes “self” proteins as foreign and activates lymphocytes to destroy them. Inactivated lymphocytes are unable to cross the blood-brain barrier, but once activated they easily cross it. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS), is an example of one such disorder. Patients display with hyperkinetic symptoms. Other examples are Basal Ganglia Encephalitis, and Sydenham Chorea. Basal Ganglia Encephalitis symptoms are dyskinesis which is the loss of voluntary movement. Sydenham Chorea causes unilateral or bilateral paralysis called chorea paralytica.

=Summary:=

In conclusion the Basal Ganglion is an important circuitry of neurons. It is essential for our ability to control movement of our body, facial, and eye muscles. It is constructed of four groups of nuclei found sub cortically. The Cerebral cortex provides stimuli that generates or suppresses movement through the direct and indirect pathways of the corticostriatal pathway. Disorders involving these pathways cause movement dysfunctions that interfere with patients’ day to day lives.

=Glossary of Terms:=

Acetylcholine Basal Ganglia Basal Ganglia Encephalitis Caudate Corpus Striatum Dopamine Globus Pallidus pars Externa Globus Pallidus pars Interna Glutamic Acid Huntington’s disease Mediodorsal Nuclei of the Thalamus Parkinson’s disease Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus Pedunclopontine Nucleus Putamen Substantia Nigra pars Compacta Substantia Nigra pars Reticulata Subthalamic Nuclei Superior Colliculus Sydenham Chorea Ventral Anterior Nuclei of the thalamus Ventral Lateral Nuclei of the thalamus γ-Aminobutyric Acid

=Review Questions:=

1. The Corpus Striatum includes what nuclei?
 * 1) A. Putamen
 * 2) B. Substantia Nigra pars Compacta
 * 3) C. Caudate
 * 4) D. A & B
 * 5) E. A & C
 * 6) F. B & C
 * 7) G. All of the above
 * 8) H. None of The above

2. All of the below receive basal ganglion output __except__?
 * 1) A. Cortex
 * 2) B. Red Nuclei
 * 3) C. Superior Colliculus
 * 4) D. Pedunclopontine Nucleus

3. Which disorders cause a loss of movement?
 * 1) A. Parkinson’s disease
 * 2) B. Huntington’s Disease
 * 3) C. Saccadic Eye Movement Disorders
 * 4) D. Basal Ganglia Encephalitis
 * 5) E. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus
 * 6) F. Sydenham Chorea
 * 7) G. A, D, & F
 * 8) H. B, C, & E

4. The input to the striatum comes from?
 * 1) A. Cerebral Cortex
 * 2) B. Red Nuclei
 * 3) C. Superior Colliculus
 * 4) D. Globus Pallidus pars Interna

5. How many Nuclei make up the basal ganglia?
 * 1) A. 2
 * 2) B. 3
 * 3) C. 4
 * 4) D. 5
 * 5) E. 6

Short Answer 6. Describe the flow of the indirect pathway? 7. Describe the flow of the direct pathway? 8. What is the importance of the Substantia Nigra pars Compacta?

=Answers:=


 * 1) 1. F
 * 2) 2. B
 * 3) 3. G
 * 4) 4. A
 * 5) 5. C
 * 6) 6. From the corpus striatum innervates the globus pallidus pars externa with GABA. The globus pallidus pars externa projects to the subthalamic nuclei with GABA. The subthalamic nuclei project to the globus pallidus pars interna and the substantia nigra pars reticulata with glutamic acid. Inhibiting the thalamus.
 * 7) 7. From the corpus striatum innervates the globus pallidus pars interna and the substantia nigra pars reticulata with GABA. The output nuclei are inhibited, which disinhibits the thalamus.
 * 8) 8. Dopamine inhibits the indirect pathways and excites the direct pathway, allowing movement generation.

=Literature Cited:=
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 * 4) **Kandel ER, Schwartz JH, Jessell TM.** //Principles of neural science//. 4th ed. New York: McGraw-Hill, 2000.
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 * 6) **Rosenblatt A, Leroi I.** Neuropsychiatry of huntington’s disease and other basal ganglia disorders. //Psychosomatics// 41: 24-30, 2000.
 * 7) **Rothwell JC.** The motor functions of the basal ganglia. //Journal of Integrative Neuroscience// 10: 303-315, 2011.
 * 8) **Weicker H, Kinscherf R, Diserens K, Deigner HP, Strüder HK.** Physiology and pathophysiology of basalganglia: impact on motor system function. //European Journal of Sport Science// 1: 1-46, 2001.