Parkinsons Disease Flashcards

1
Q

The basal ganglia are a group of nuclei located in the base of forebrain and top of midbrain. Using the labels below label the basal ganglia:

  • Caudate Nucleus
  • Putamen
  • Internal Globus pallidus
  • External Globus pallidus
A

1 - caudate nucleus
2 - putamen
3 - external globus pallidus
4 - internal globus pallidus

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2
Q

What is the main function of the basal ganglia?

1 - control of movement and motor learning
2 - emotion
3 - memory and learning
4 - sensory processing

A

1 - control of movement and motor learning
- part of the extrapyramidal tracts

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3
Q

What is the name given to caudate nucleus and the putamen when they are combined?

1 - substantia niagra
2 - neostriatum
3 - vermis
4 - amygdala

A

2 - neostriatum

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4
Q

There are 2 ganglia that have a close anatomical and functional relationship with the neostriatum (Caudate nucelus and putamen) and the internal and external Globus pallidus, and are included in the group of cell nuclei called the basal ganglia. What are the 2 additonal ganglia called?

1 - substantia nigra
2 - subthalamic nucleus
3 - thalamus
4 - nucleus accumbans

A

1 - substantia nigra
2 - subthalamic nucleus

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5
Q

The caudate nucleus is C shaped and contains the head, body and tail and follows a similar course to what in the brain?

1 - lateral ventricle
2 - 3rd ventricle
3 - thalamus
4 - brain stem

A

1 - lateral ventricle

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6
Q

The caudate nucleus is C shaped and contains the head, body and tail and follows the course of the lateral ventricle. What is at the end of the tail of the caudate nucleus?

1 - hypothalamus
2 - amygdala
3 - thalamus
4 - somatosensory cortex

A

2 - amygdala

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7
Q

The internal capsule is a white matter structure situated in the inferior medial part of each cerebral hemisphere of the brain, do the following sit medially or laterally to it:

  • Caudate Nucleus
  • Putamen
  • Internal Globus pallidus
  • External Globus pallidus
A
  • Caudate Nucleus = medial
  • Putamen = lateral
  • Internal Globus pallidus = lateral
  • External Globus pallidus = lateral
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8
Q

The substantia nigra (latin for black substance) is composed of 2 regions, what are they called?

1 - pars reticulata and amygdala
2 - pars reticulata and caudate nucleus
3 - pars compacta and pars compacta
4 - pars compacta and pars reticulata

A

4 - pars compacta and pars reticulata

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9
Q

There are 2 parts to the substantia nigra:
- pars compacta
- pars reticulata
-
Which of these 2 regions is responsible for producing the majority of the dopamine?

A
  • pars compacta
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10
Q

Where does the largest afferent (information directed to the basal ganglia) source for the basal ganglia come from?

1 - cerebral cortex
2 - frontal cortex
3 - occipital cortex
4 - somatosensory cortex

A

1 - cerebral cortex
- specifically the motor sensory and limbic areas

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11
Q

Within the basal ganglia, which 2 parts receive the majority of afferent (information directed to the basal ganglia) stimulus?

1 - globus pallidus and putamen
2 - globus pallidus and caudate
3 - caudate and putamen
4 - caudate and substantia niagra

A

3 - caudate and putamen (together they may up the striatum)

  • putamen (somatosensory, primary motor cortex)
  • caudate (pre frontal and limbic regions)
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12
Q

There are multiple connections within the basal ganglia, and these can be direct or indirect. Are both of these excitatory?

A
  • no
  • direct = excitatory (glutamate)
  • indirect = inhibitory (GABA)
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13
Q

The direct pathway sends excitatory projections from the cerebral cortex to where in the basal ganglia, and which neurotransmitter is involved?

1 - striatum (composed of the putamen and caudate nucleus) releasing dopamine
2 - striatum (composed of the putamen and caudate nucleus) releasing glutamate
3 - striatum (composed of the putamen and caudate nucleus) releasing serotonin
4 - striatum (composed of the putamen and caudate nucleus) releasing acetylcholine

A

2 - striatum (composed of the putamen and caudate nucleus) releasing glutamate

  • striatum (composed of the putamen and caudate nucleus)
  • glutamate is the excitatory neurotransmitter
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14
Q

In the direct pathway excitatory projections from the cerebral cortex are sent to the striatum (composed of the putamen and caudate nucleus) and the neurotransmitter glutamate is released. Where does the striatum then signal, and what type of innervation is delivered?

1 - internal globus pallidus releasing glutamate
2 - internal globus pallidus releasing GABA
3 - external globus pallidus releasing glutamate
4 - external globus pallidus releasing GABA

A

2 - internal globus pallidus releasing GABA

  • striatum to internal globus pallidus
  • inhibitory projections releasing GABA
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15
Q

In the direct pathway excitatory projections from the cerebral cortex are sent to the striatum (composed of the putamen and caudate nucleus) and the neurotransmitter glutamate is released. The striatum then sends inhibitory projections to the internal globus pallidus releasing GABA. This means the internal globus pallidus, which would generally transmit the inhibitory neuron GABA is reduced, or stopped altogether. Where does the internal globus pallidus then send projections to?

1 - hypothalamus
2 - amygdala
3 - thalamus
4 - somatosensory cortex

A

3 - thalamus

  • internal globus pallidus to the thalamus
  • no or very little GABA is released so thalamus stimulates the cortex to move
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16
Q

In the direct pathway excitatory projections from the cerebral cortex are sent to the striatum (composed of the putamen and caudate nucleus) and the neurotransmitter glutamate is released. The striatum then sends inhibitory projections to the internal globus pallidus releasing GABA. The internal globus pallidus then sends inhibitory projections to the thalamus, which is usually active releasing GABA and inhibiting excitatory projections from the thalamus to the cerebral cortex. However, if the striatum inhibits the internal globus pallidus, is the internal globus pallidus then able to inhibit the thalamus?

A
  • no
  • no or little GABA is released at the thalamus, like a tap, you can turn on or off, or medium flow relates to the amount of movement we need to elicit
  • thalamus can send excitatory projections to the cerebral cortex and stimulate movement
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17
Q

In the indirect pathway excitatory projections from the cerebral cortex are sent to the striatum (composed of the putamen and caudate nucleus) and the neurotransmitter glutamate is released. The striatum then sends inhibitory projections to the external globus pallidus releasing GABA. The external globus pallidus then sends inhibitory projections where?

1 - hypothalamus
2 - amygdala
3 - thalamus
4 - subthalamic nucleus (SN)

A

4 - subthalamic nucleus (SN)

  • GABA is released from external globus pallidus and SN is not inhibited
  • SN releases glutamate that then stimulates internal globus pallidus
  • internal globus pallidus in turn then releases GABA at thalamus and inhibits movement
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18
Q

In the indirect pathway excitatory projections from the cerebral cortex are sent to the striatum (composed of the putamen and caudate nucleus) and the neurotransmitter glutamate is released. The striatum then sends inhibitory projections to the external globus pallidus releasing GABA. The external globus pallidus then send inhibitory projections to the subthalamic nucleus, which is always active. However, if the striatum inhibits the external globus pallidus, is the external globus pallidus then able to inhibit the subthalamic nucleus?

A
  • no
  • subthalamic nucleus can continue send excitatory projections through the release of GABA
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19
Q

In the indirect pathway excitatory projections from the cerebral cortex are sent to the striatum (composed of the putamen and caudate nucleus) and the neurotransmitter glutamate is released. The striatum then sends inhibitory projections to the external globus pallidus releasing GABA. The external globus pallidus then send inhibitory projections to the subthalamic nucleus, which is always active. However, when the striatum inhibits the external globus pallidus, the external globus pallidus is unable to inhibit the subthalamic nucleus. The subthalamic nucleus can then send excitatory projections where?

1 - external globus pallidus
2 - internal globus pallidus
3 - thalamus
4 - subthalamic nucleus (SN)

A

2 - internal globus pallidus

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20
Q

In the indirect pathway excitatory projections from the cerebral cortex are sent to the striatum (composed of the putamen and caudate nucleus) and the neurotransmitter glutamate is released. The striatum then sends inhibitory projections to the external globus pallidus releasing GABA. The external globus pallidus then send inhibitory projections to the subthalamic nucleus, which is always active. However, when the striatum inhibits the external globus pallidus, the external globus pallidus is unable to inhibit the subthalamic nucleus. The subthalamic nucleus can then send excitatory projections to the internal globus pallidus. If the internal globus pallidus is being excited, what can this then inhibit?

1 - external globus pallidus releasing GABA
2 - internal globus pallidus releasing GABA
3 - substantia niagra releasing GABA
4 - thalamus releasing GABA

A

4 - thalamus releasing GABA
- thalamus is then inhibited and movements we dont want are stopped
- indirect pathway does the opposite of the direct pathway

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21
Q

In addition to receiving excitatory projections from the cerebral cortex, in the direct pathway where else, that is associated with the basal ganglia is able to send projections to the striatum (composed of the caudate nucleus and putamen), and what neurotransmitter is released?

1 - external globus pallidus releasing dopamine
2 - internal globus pallidus releasing dopamine
3 - substantia niagra releasing dopamine
4 - thalamus releasing dopamine

A

3 - substantia niagra releasing dopamine

  • specifically the pars compacta
  • dopamine binds to D1 receptors exciting striatum
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22
Q

In addition to receiving excitatory projections from the cerebral cortex, the substantia nigra sends projections to the striatel cells of the striatum releasing dopamine. Dopamine is able to initiate 2 actions, what are they and why?

A
  • both inhibitory and excitatory
  • D1 receptors = excitatory (Gas GPCR)
  • D2 receptors = inhibitory (Gai GPCR)
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23
Q

In addition to receiving excitatory projections from the cerebral cortex, the substantia nigra sends projections to the striatel cells of the striatum releasing dopamine. Dopamine is able to initiate both inhibitory and excitatory actions, depending on whether it binds with D1 receptors = excitatory or D2 receptors = inhibitory. If D1 receptors bind dopamine, does this activate the direct or indirect pathway?

A
  • activates the direct pathway
  • means we can move the muscle we want to move
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24
Q

In addition to receiving excitatory projections from the cerebral cortex, the substantia nigra sends projections to the striatel cells of the striatum releasing dopamine. Dopamine is able to initiate both inhibitory and excitatory actions, depending on whether it binds with D1 receptors = excitatory or D2 receptors = inhibitory. If D2 receptors bind dopamine, does this activate the direct or indirect pathway?

A
  • enhances the indirect pathway
  • inhibits movement we dont want to happen
  • in Parksinsons disease, the loss of dopamine means patients have movements they do not want to happen
25
Q

What gives the substantia nigra its dark colour?

A
  • large concentration of dopamine producing neurons
  • produce most of dopamine in the brain
26
Q

What is the 1st and 2nd most common neurological disorder?

A
  • 1st is Alzheimers (form of dementia)
  • 2nd is Parkinsons disease
27
Q

In Parkinsons disease there is atrophy of the substantia nigra, specifically the pars compacta region. What is the normal role of pars compacta of the substantia nigra in the direct pathway in the basal ganglia?

1 - dopamine released binds D1 (excite direct) and D2 (excite indirect) pathways
2 - dopamine released binds D2 (excite direct) and D1 (excite indirect) pathways
3 - dopamine released binds D1 (inhibits direct) and D2 (inhibits indirect) pathways
4 - dopamine released binds D1 exciting direct and indirect pathways

A

1 - dopamine released binds D1 (excite direct) and D2 (excite indirect) pathways

  • pars comparta synapes with striatum and releases dopamine
  • binding D1 receptors dopamine ensures voluntary movement through enhancement of direct pathway
  • dopamine binds D2 receptors and indirect pathway. Essentially patients are not able to inhibit unwanted movements
28
Q

Parkinsons is often described as a hypokinetic disease, why is this?

A
  • low or no movement
  • often patients have movements they don’t want, such as the pill rolling tremor
  • low/no dopamine stimulating striatum from substantia nigra compacta
  • thalamus may be inhibited and decrease movement
29
Q

What is the prevalence of Parkinsons disease in the UK?

1 - 1300
2 - 33,000
3 - 137,000
4 - 250,000

A

3 - 137,000

  • incidence is 33.4 per 100,000
  • 17,300 new diagnoses/ year in >45s
  • lifetime risk 2.7%
30
Q

Is Parkinsons more common in men or women?

A
  • men
31
Q

Lewy bodies have been linked with the pathophysiology of Parkinsons disease. What are Lewy bodies?

1 - aggregates of proteins called tau protein
2 - aggregates of proteins called B amyloid
3 - aggregates of proteins called a-synuclein
4 - aggregates of proteins called BDNF

A

3 - aggregates of proteins called a-synuclein
- adhere to nerves and damage them, impairing their function

32
Q

Are lewy bodies (aggregates of proteins called a-synuclein) are present in Parkinsons disease. However, they are not unique to Parkinsons. Which other condition are Lewy bodies present in?

1 - Alzheimer’s
2 - Frontal Lobe Dementia
3 - Lewy Body Dementia
4 - Vascular Dementia

A

3 - Lewy Body Dementia
- common in parkinsons disease in substantia nigra
- common in other neurological disorders such as Lewy body dementia
- dementia with lewy bodies found throughout the cerebral cortex

33
Q

Patients with parkinsons disease present with clinical symptoms when they have lost aprox what percentage of niagral neurons?

1 - 10-20%
2 - 30-50%
3 - 60-70%
4 - 70-80%

A

4 - 70-80%

34
Q

Does the risk of developing parkinsons disease increase or decrease with age?

A
  • increases with age
  • median age 45-65 year, with a mean of 60 years old
35
Q

Which of the following is NOT a core symptom of Parkinsons disease?

1 - tremor (often described as pill rolling)
2 - rigidity (stiff muscles)
3 - akinesia (slowing of movement)
4 - hyperkinesia
5 - postural abnormalities

A

4 - hyperkinesia
- remember the mnemonic TRAP:
- T = tremor
- R = rigidity
- A = akinesia (absence of movement)
- P = postural abnormalities

36
Q

In Parkinsons disease, there are common motor-function symptoms:

  • T = tremor
  • R = rigidity
  • A = akinesia (absence of movement)
  • P = postural abnormalities

Are these symptoms bilateral or unilateral?

A
  • typically unilateral
  • if bilateral, suspect other causes
37
Q

In addition to the common motor-function symptoms of Parkinsons disease, all of the following are common, EXCEPT which one?

1 - diarrhoea
2 - postural hypotension
3 - urinary frequency/dribbling
4 - reduced sense of smell
5 - sleep disturbance
6 - depression
7 - psychosis

A

1 - diarrhoea
- typically causes constipation

38
Q

When diagnosing Parkinsons disease we can use the brain bank criteria. What is stage 1 of this criteria to diagnose parkinsons syndrome?

1 - patient must have all of the following: 1 - tremor, rigidity, bradykinesia and postural instability (PI)
2 - patient must have bradykinesia and 1 of the following: rigidity, resting tremor and PI
3 - patient must have PI and rigidity
4 - patient must have brain biopsy with the presence of Lewy bodies

A

2 - patient must have bradykinesia and 1 of the following: rigidity, resting tremor or PI

Step 2 is:
- History and examination findings pointing to an alternative diagnosis

39
Q

Which imaging modality can help in confirming a diagnosis of Parkinsons disease?

1 - MRI
2 - X-ray
3 - CT
4 - PET

A

4 - PET

40
Q

Which of the following is NOT a differential for Parkinsons disease?

1 - Vascular Parkinsonism
2 - Drug-induced Parkinsonism
3 - Alzheimer’s
4 - Dementia with Lewy bodies

A

3 - Alzheimer’s

41
Q

What scale can be used to identify the functional disability associated with Parkinsons disease?

1 - Modified Hoehn & Yahr Scale
2 - Rockwood Scale
3 - Geriatric Movement Scale
4 - Modified Glasgow Scale

A

1 - Modified Hoehn & Yahr Scale

42
Q

What is the key Parkinsons disease medication that we need to be aware of as a key drug?

1 - Levodopa
2 - Gabapentin
3 - Entacapone
4 - Carbidopa

A

1 - Levodopa also known as L-DOPA
- patients typically have a good response to L-DOPA, but can cause dyskinesia, involuntary, erratic, writhing movements of the face, arms, legs or trunk. Involuntary, erratic, writhing movements of the face, arms, legs or trunk.

43
Q

Levodopa also known as L-DOPA is the core drug for treating parkinsons disease that we need to be aware of. How does this drug increase dopamine levels?

1 - converted to dopamine in liver as prodrug and then enters the brain
2 - enters the brain via the venous retrun
3 - L-DOPA can cross the BBB and is then converted into dopamine
4 - all of the above

A

3 - L-DOPA can cross the BBB and is then converted into dopamine
- dopamine cannot be administered as it cannot pass the BBB
- dopamine increases dopamine levels in striatum

44
Q

Does the effectiveness of drugs for Parkinsons disease, such as Levodopa also known as L-DOPA maintain its effectiveness over time?

A
  • no
  • patients doses typically increase over time and become more frequent
45
Q

How is L-DOPA (levodopa) converted into dopamine in the brain?

1 - DOPA carboxylase
2 - L-DOPA hydroxyase
3 - carboxylase
4 - lactate dehydrogenase

A

1 - DOPA carboxylase

46
Q

Carbidopa is often given alongside Levodopa, the core drug for parkinsons disease. Why is this drug given alongside Levodopa?

1 - able to cross BBB and increase dopamine production
2 - inhibits dopamine carboxylase in peripheries, ensuring it all goes to the brain
3 - inhibits Levodopa from creating too much dopamine
4 - binds to BBB and assists dopamine in crossing BBB

BBB = blood brain barrier

A

2 - inhibits dopamine carboxylase in peripheries, ensuring it all goes to the brain
- ensure Levodopa all goes to the brain and crosses the BBB

47
Q

Sinemet is a combination of L-DOPA and carbidopa. It is very effective in Parkinsons disease for what?

1 - curing parkinsons
2 - reversing parkinsons but not curing it
3 - effective symptom relief through dopamine optimisation
4 - all of the above

A

3 - effective symptom relief through dopamine optimisation

48
Q

In addition to Levodopa, we need to be aware of a second core drug that is used to treat parkinsons disease patients. What is this drug called and what is its mechanism of action?

1 - Ropinirole
2 - Gabapentin
3 - Entacapone
4 - Carbidopa

A

1 - Ropinirole

  • dopaminergic agonist
  • stimulates dopaminergic receptors and often used alongside Levodopa
49
Q

Although dopaminergic drugs can be beneficial for parkinsons disease, there are adverse events. What are the common side effects of L-DOPA (Levodopa)?

1 - GIT symptoms and motor fluctuations
2 - GIT and dyskinesias-hyperkinetic involuntary movements
3 - dyskinesias-hyperkinetic involuntary movements and motor fluctuations
4 - dyskinesias-hyperkinetic involuntary movements and short term anxiety

A

3 - dyskinesias-hyperkinetic involuntary movements and motor fluctuations

  • essentially this is caused by over stimulation of the direct pathway by too much dopamine binding with D1 receptors on the striatum
50
Q

Although dopaminergic drugs can be beneficial for parkinsons disease, there are adverse events. What are the 2 common side effects of dopaminergic agonists, specifically Ropinirole?

1 - GIT symptoms and impulse control disorders (failure to resist temptation)
2 - GIT and dyskinesias-hyperkinetic involuntary movements
3 - psychosis and motor fluctuations
4 - impulse control disorders (failure to resist temptation) and psychosis

A

4 - impulse control disorders (failure to resist temptation) and psychosis

  • impulse control disorders (failure to resist temptation)
  • psychosis - linked with increased dopamine in mesolimbic pathway
51
Q

What is the most common alternatives to dopinergic agonists Ropinirole and L-DOPA
(Levodopa) in the treatment of Parkinsons disease?

1 - acetylcholine
2 - epileptic medication
3 - gabapentin
4 - anti-cholinergics

A

4 - anti-cholinergics

  • ACh can be high in Parkinsons disease and cause cytotoxicity
  • block the action of ACh
  • high ACh in Parkinsons disease has been linked with dyskinesia
52
Q

Catechol-O-methyltransferase (COMT) is an enzyme that is able to degrade a number of monoamines. Inhibitors of COMT can be given alongside Levodopa (L-DOPA). What is the mechanisms of action and what is the core drug we need to know?

1 - entacapone
2 - Ibuprofen
3 - Aripiprazole
4 - Haloperidol

  • all inhibit COMT so dopamine is not metabolised
A

1 - entacapone

  • inhibits enzyme COMT, so dopamine is not metabolised
  • extends the benefits of Levodopa (L-DOPA)
53
Q

Monoamine Oxidase B (MAO-B), is an enzyme that is able to metabolise dopamine. MAO-B inhibitors can be given alongside Levodopa (L-DOPA). What is the mechanisms of action and what is the core drug we need to know?

1 - entacapone
2 - Ibuprofen
3 - aripiprazole
4 - seligiline

  • all inhibit MAO-B so dopamine is not metabolised
A

4 - seligiline

  • inhibitor of MAO-B, blocking central dopamine metabolism
  • improves response to L-DOPA
54
Q

Rasagililine can be given alongside Levodopa (L-DOPA). What is the mechanisms of action and what is the core drug we need to know?

1 - inhibits dopamine re-uptake in the synaptuc cleft
2 - inhibits MOA-B and therefore reduces metabolism of dopamine and raises dopamine levels
3 - agonist on Ca2+ on pre-synapse and increases stimulation to release dopamine
4 - all of the above

A

-2 - inhibits MOA-B and therefore reduces
- irreversible inhibitor of monoamine oxidase-B (MOA-B)
- blocks central dopamine metabolism
- can improve response to Levodopa (L-DOPA)

55
Q

The direct pathway increases movement and the indirect pathway inhibits movement. How can we apply this to a healthy person who wants to contract his bicep?

A
  • bicep contraction = direct pathway stimulated
  • tricep relaxation = indirect pathway stimulated
56
Q

In parkinsons disease the substantia nigra is not functioning properly and we have less dopamine. What can then happen in the direct pathway, which generally increases movement?

1 - less stimulation of striatum (glutamate = excitatory)
2 - less inhibition of globus pallidus internal (GPI), which therefore increases more GABA
3 - large amounts of GABA from GPI inhibit the thalamus, reducing glutamate release to cerebral cortex
4 - abnormal, slow or no movement
5 - all of the above

A

5 - all of the above

57
Q

In parkinsons disease the substantia nigra is not functioning properly and we have less dopamine. What can then happen in the indirect pathway, which generally increases unwanted movement?

1 - less stimulation of striatum (dopamine = inhibitory)
2 - less inhibition of globus pallidus external (GPE)
3 - GPE increases release of GABA at the synapse with the sub-nucleus (SN)
4 - SN releases low glutamate and no stimulation of the internal globus pallidus (GPI)
5 - GPI is not excited so low GABA released at thalamus, and thalamus is able to excite the motor cortex with glutamate
6 - abnormal or unwanted movement occurs
7 - all of the above

A

7 - all of the above

58
Q

In parkinsons disease the substantia nigra is not functioning properly and we have less dopamine. What can then happen overall to the direct and indirect pathways?

A
  • direct = inhibited due to lack of dopamine = less movement
  • indirect = reduced inhibition = more unwanted movements
  • essentially causes akinesia and bradykinesia