Parkisons Part 1 (Basal Ganglia)

Question 1

What are the four main parts of the basal ganglia?

Answer 1

The four main parts are the Striatum (caudate and putamen), Globus Pallidus (external and internal segments), Substantia nigra (pars compacta and pars reticulata), and Subthalamic nucleus.

Question 2

What is the role of the basal ganglia in movement?

Answer 2

The basal ganglia influence movement by modulating activity in upper motor neurons.

Question 3

What is the striatum in the basal ganglia?

Answer 3

The striatum is the largest component and includes the caudate nucleus and the putamen.

Question 4

What are the main input areas to the basal ganglia?

Answer 4

Striatum (caudate and putamen) receiving inputs from most of the cerebral cortex and other regions.

Question 5

What type of neurons receive cortical signals in the basal ganglia?

Answer 5

“Medium spiny neurons” in the basal ganglia receive cortical signals.

Question 6

For the control of limb movements, where does the output from the basal ganglia arise, and where is it sent?

Answer 6

For the control of limb movements, the output from the basal ganglia arises in the internal segment of the globus pallidus and is sent to the ventral anterior and ventral lateral nuclei (VA/VL complex) of the thalamus.

Question 7

What are the two main output structures from the basal ganglia?

Answer 7

The main output structures are the Globus Pallidus (internal segment) and the substantia nigra (pars reticulata).

Question 8

Where does the output from the substantia nigra (pars reticulata) go for eye movements?

Answer 8

Projects to upper motor neurons in the superior colliculus and controls orienting movements of the eyes and head.​

Question 9

What kind of inputs do the Input Nuclei of the basal ganglia receive?

Answer 9

These nuclei receive prominent excitatory inputs (glutamertergic) from the cerebral cortex, thalamus, subthalamus, substantia nigra, and brainstem structures.

Question 10

What are smaller but functionally significant components of the basal ganglia system? Where do they provide input to?

Answer 10

Substantia nigra pars compacta and the subthalamic nucleus, which provide input to the striatum and pallidum

Question 11

What is the name of the pathway through which cortical signals reach the basal ganglia?

Answer 11

The pathway is called the “corticostriatal pathway.”

Question 12

Two main outputs from basal ganglia

Answer 12

1) To motor areas via the thalamus from from Globus Pallidus (int.)
2) To eye mvt areas of brainstem​ from substantia nigra (pars reticulata) ​

Question 13

What are the two main groups of projection neurons in the striatum?

Answer 13

The two main groups of projection neurons in the striatum are those that project to the GP(int) and SN pars reticulata (forming the direct pathway) and those that project to GP(ext) (forming the indirect pathway).

Question 14

What type of projections do medium spiny neurons of the caudate and putamen give rise to?

Answer 14

Inhibitory GABAergic projections to the globus pallidus and substantia nigra pars reticulata.

Question 15

How does the striatum’s excitation influence movement initiation?

Answer 15

Excitement in the striatum inhibits the tonically active cells in the globus pallidus and substantia nigra, which usually suppress movement. This leads to the disinhibition of thalamic neurons and triggering movement initiation.

Question 16

What is the pattern of activity in the Globus Pallidus internal segment (GPi) and substantia nigra during rest?

Answer 16

The GPi and substantia nigra often exhibit spontaneous activity during rest.

Question 17

What is the primary function of the direct pathway in the basal ganglia?

Answer 17

The direct pathway decreases tonic inhibitory output from the basal ganglia (means BG is less actively inhibiting certain brain regions, allowing those regions to become more active and promote movement or action)

Question 18

What is the primary function of the indirect pathway in the basal ganglia?

Answer 18

The indirect pathway increases tonic inhibitory output from the basal ganglia (means the BG is more actively inhibiting certain brain regions, reducing their activity and potentially suppressing movement or action)

Question 19

How does the function of the indirect pathway compare to that of the direct pathway?

Answer 19

While the direct pathway encourages action, the indirect pathway advises against certain actions and inhibits movement.

Question 20

Describe the indirect pathway within the basal ganglia.

Answer 20

1. Motor cortex sends excitatory signals to the striatum
2. Striatum sends inhibtory signals to the the global pallidus (ext)
3. Global pallidus ext sends inhibitory neurons to subthalamic nucleus
4. The subthalmaic nucleus sends excitatory neurons back to the Gp (int) and the substania niagara
   5.These two sends inhibitory signals to the thalamus which sends excitatory signals to the motor cortex

Question 21

How does the subthalamic nucleus influence the basal ganglia’s output?

Answer 21

The subthalamic nucleus influences the basal ganglia’s output by exciting the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr), which leads to increased inhibition of the thalamus.

Question 22

What determines the output from the pallidum to the thalamus or superior colliculus?

Answer 22

The output from the globus pallidus to the thalamus or superior colliculus is determined by the balance of excitatory (from the subthalamic nucleus) and inhibitory (from the striatum) inputs. These inputs modulate the activity of the globus pallidus, regulating its output to the thalamus or superior colliculus.

Question 23

What causes the differential effects of dopamine in the basal ganglia?

Answer 23

The differential effects of dopamine are due to the presence of different dopamine receptor subtypes.

Question 24

How does dopamine affect medium spiny neurons in the striatum?

Answer 24

Dopamine, originating from the substantia nigra pars compacta, modulates glutamatergic inputs from the cortex and excites spiny cells through D1 receptors.

Question 25

How does dopamine affect the direct and indirect pathways through D1 and D2 receptors?

Answer 25

1) D1 receptors, excited by dopamine, enhance the direct pathway, promoting the initiation of voluntary movements.
2) D2 receptors, inhibited by dopamine, reduce the inhibitory influence of the indirect pathway, allowing for smoother execution of motor commands.
3) Dopamine promotes the selection and initiation of purposeful movements (via the direct pathway) while simultaneously inhibiting unwanted or competing movements (via the indirect pathway)

Question 26

3 Potential Treatments for Parkinson’s

Answer 26

1) Deep Brain Stimulation
2) Gene Therapy
3) Stem Cell Grafts

Question 27

What is Deep Brain Stimulation (DBS), and how is it used to treat PD?

Answer 27

Implanting electrodes in specific brain areas; targeting areas like the subthalamic nucleus, is used to normalize neural activity in the basal ganglia circuits, improving motor function in Parkinson’s patients.

Question 28

How can gene therapy potentially treat Parkinson’s disease?

Answer 28

Boost dopamine in the brain by inserting genes for the enzyme tyrosine hydroxylase, which helps make dopamine, a key neurotransmitter for movement.

Question 29

What are stem cell grafts and how can they be used in Parkinson’s disease treatment?

Answer 29

Using versatile stem cells to create new dopamine-producing neurons in the brain, offering a potential way to replace damaged neurons and improve symptoms in Parkinson’s disease

Question 30

What is the major function of the basal ganglia?

Answer 30

The major function of the basal ganglia is believed to be the “Focused Selection” of an action.

Question 31

What does focused selection in the basal ganglia describe?

Answer 31

Focused selection describes the outcome of two parallel processes that act together: the facilitation (selection) of the desired output or action, and the suppression of undesired outputs or actions.

Question 32

How are the facilitation and suppression processes in the basal ganglia realized?

Answer 32

The facilitation and the suppression processes are realized by two different pathways through the basal ganglia, called the direct and the indirect pathway.

Question 33

What does the Direct Pathway in the basal ganglia correspond to?

Answer 33

The Direct Pathway corresponds to the basic disinhibitory circuit, which includes the caudate/putamen, the globus pallidus interna, and the ventral thalamus.

Question 34

What does the activation of the indirect pathway by the striatum do?

Answer 34

Drives neurons in a “surround” region of the internal segment of the globus pallidus by excitatory inputs from the subthalamic nucleus, reinforcing the suppression of competing motor programs.

Question 35

What does the activation of the direct pathway by the striatum do?

Answer 35

Activation of the direct pathway causes focal inhibition of a “center” cluster of neurons in the internal segment, resulting in the disinhibition of the VA/VL complex and the expression of the intended motor program.

Question 36

Give examples of motor vs non-motor symptoms in Parkisons

Answer 36

1) Motor: Bradykinesia (slow and reduced movements), tremors, walking/gait difficulties, dystonia (involuntary muscle contractions)
2) Non-motor: loss of smell, depression/anxiety, joint pain/sleep difficulties

Question 37

What are typical motor symptoms in the mild stage of Parkinson’s disease? (5)

Answer 37

Limited arm swing while walking, facial expression difficulty, heavy legs, stooped posture, smaller handwriting, stiffness, and tremors on one side of the body.

Question 38

What motor symptoms are seen in the moderate stage of Parkinson’s disease?

Answer 38

The moderate stage includes symptoms such as speech changes, freezing mid-movement, swallowing difficulty, increased falls, and small, shuffling steps.

Question 39

What are the motor symptoms in the advanced stage of Parkinson’s disease?

Answer 39

Individuals may be bedridden or wheelchair-bound, unable to live independently, suffer from severe posture issues, and require help with daily tasks.

Question 40

What is the principle of disinhibition?

Answer 40

Refers to the process where the inhibition of an inhibitory signal results in the activation of neurons, allowing for controlled movement initiation.

Question 41

Explain the simplified basal ganglia diagram and how the basal ganglia modulate movement through a balance of excitatory and inhibitory signals:

Answer 41

1) The striatum receives excitatory inputs from the cortex and processes this information.
2) It then sends inhibitory signals to the GPi and SNr.
3) The GPi and SNr are the major output centers of the basal ganglia and usually send inhibitory signals to their targets.
3) When the striatum inhibits these output centers, it results in less inhibition (disinhibition) of the thalamus and superior colliculus.
4) Disinhibition of the thalamus allows it to activate the frontal cortex, facilitating movement.
5) The SNr also sends inhibitory signals to the superior colliculus, which is involved in eye movement control.

Question 42

Describe the Direct pathway for Basal Ganglia involvement according to the Standard Model

Answer 42

1. Initiation of Movement: The cortex sends excitatory signals to the striatum (composed of the caudate nucleus and putamen).
2. Inhibition of Inhibition: The striatum inhibits the globus pallidus internal (GPi) and substantia nigra pars reticulata (SNr), which are normally inhibitory to the thalamus.
3. Facilitation of Movement: With GPi/SNr inhibited, the thalamus is disinhibited and can send excitatory signals back to the cortex, facilitating movement.

Question 43

What happens in the disinhibitory circuit when the striatal neurons are at rest?

Answer 43

When striatal neurons are at rest, the globus pallidus exhibits high tonic activity and continuously inhibits the output neurons in the thalamus, preventing the initiation of motor commands.

Question 44

What is the effect of diminished dopaminergic inputs from the substantia nigra pars compacta in Parkinson’s disease on the motor pathways?

Answer 44

In Parkinson’s disease, reduced dopamine from the substantia nigra pars compacta disrupts the brain’s ability to control movements. This imbalance affects the direct pathway, making it harder to start movements, and the indirect pathway, which becomes overactive and inhibits movement.

Question 45

Parkinson’s disease is characterized by two key histological features in brain tissue sections?

Answer 45

1) Loss of Dopamingeric neurons: In the substantia nigra pars compacta, the degeneration of dopaminergic neurons can disrupt melanin regulation, leading to changes in the substantia nigra’s color, making it appear more brown.
2) Presence of abnormal protein clusters called Lewy bodies (composed of misfolded alpha-synuclein) within cells

Question 46

How do Lewy bodies contribute to the progression of Parkinson’s disease?

Answer 46

The accumulation of Lewy bodies disrupts normal cellular function and is associated with the death of dopaminergic neurons, leading to dopamine deficiency and motor symptoms characteristic of Parkinson’s disease.

Question 47

What are ‘Distribution Pathways’ in Parkinson’s disease?

Answer 47

‘Distribution Pathways’ refer to the routes such as nerves or blood vessels through which Parkinson’s disease-related proteins or inflammatory signals may travel from the gut to the brain.

Question 48

What role does the vagus nerve (N. vagus) play in the development of Parkinson’s disease?

Answer 48

The vagus nerve may serve as a route for alpha-synuclein, a protein linked to the disease, to travel from the gut directly to the brainstem, potentially initiating the disease.

Question 49

How might the bloodstream contribute to the origin of Parkinson’s disease?

Answer 49

The bloodstream could carry inflammatory molecules or harmful proteins (alpha synuclein) from the gut to the brain, which may contribute to the onset of Parkinson’s disease.

Question 50

What is the significance of Alpha-Synuclein in Parkinson’s disease?

Answer 50

When alpha-synuclein misfolds, it sticks together to form clumps in the brain, which can damage and kill nerve cells that produce dopamine, leading to the symptoms of Parkinson’s disease.

Question 51

What are the two main hypotheses regarding the onset of Parkinson’s disease?

Answer 51

1. Alpha-synuclein hypothesis: This theory suggests that Parkinson’s disease begins with the accumulation of abnormal alpha-synuclein protein in the brain, leading to the formation of Lewy bodies, which are associated with the death of dopamine-producing neurons.
2. The gut-brain hypothesis suggests that Parkinson’s disease may start in the gut due to inflammation or changes in gut bacteria, signaling to the brain through the vagus nerve.

Question 52

What does synucleopathy describe in the context of Parkinson’s disease?

Answer 52

Describe a group of neurodegenerative disorders characterized by the abnormal accumulation of alpha-synuclein protein in neurons

Question 53

What are the origins of Parkinson’s disease (PD)? (5)

Answer 53

1. The gut to brain hypothesis​
2. Distribution pathways​
3. N. vagus​
4. Bloodstream​
5. Alpha-Synuclein

Question 54

How do preganglionic and postganglionic fiber lengths differ between the sympathetic and parasympathetic nervous systems?

Answer 54

The sympathetic nervous system has short preganglionic and long postganglionic fibers leads to the effector organs. The parasympathetic pathway generally involves a long preganglionic fiber reaching close to the target effector organ and then a short postganglionic fiber that connects to the organ itself.

Question 55

How are the brain and spinal cord connected to the gut?

Answer 55

The brain and spinal cord are linked to the gut through nerves, mainly the vagus nerve for ‘rest and digest’ functions, and sympathetic nerves for ‘fight or flight’ responses.

Question 56

How does the vagus nerve communicate with the gut?

Answer 56

The vagus nerve sends signals directly to the gut, influencing its function and activity. This direct communication helps regulate various gut processes, including digestion and nutrient absorption.

Question 57

What are the two important nerve networks inside the gut wall?

Answer 57

Inside the gut wall, there are two main nerve networks: the myenteric (Auerbach’s) plexus and the submucous (Meissner’s) plexus. These networks play crucial roles in regulating gut function.

Question 58

What is the function of the myenteric plexus? Where is it located?

Answer 58

The myenteric plexus is located between the circular and longitudinal muscle layers of the gut. It controls muscle contractions that move food along the gut, ensuring proper digestion and absorption of nutrients.

Question 59

What is the function of the submucous plexus?

Answer 59

The submucous plexus in the gut’s inner wall regulates enzyme secretion, blood flow, and ion transport, optimizing digestion and nutrient absorption.

Question 60

Which brain pathways are affected in the early stages of Parkinson’s Disease?

Answer 60

The nigrostriatal pathway, which is crucial for controlling voluntary movements, is affected in the early stages of Parkinson’s Disease.

Question 61

As Parkinson’s Disease progresses, which additional brain pathways become affected?

Answer 61

The mesocortical and mesolimbic pathways (related to cognition, emotion, and reward) and the tuberoinfundibular pathway (related to hormone regulation) are also affected. ​