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Neuroscience Exam 2 > Lecture 8: Basal Ganglia > Flashcards

Lecture 8: Basal Ganglia Flashcards

1
Q

What is the function of the basal ganglia?

A

Influence movement by regulating activity of upper motor neurons

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2
Q

True or False. The Basal Ganglia projects directly on lower motor neurons

A

False

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3
Q

List the motor components of the basal ganglia (4)

A
  • Straitum
    1. Caudate
    2. Putamen
  • Globus padillus (Internal and external portions)
  • Subthalamic nucleus
  • Substantia nigra (located in the brain stem)
    1. Pars compacta
    2. Pars reticulata
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4
Q

What do motor components of the basal ganglia and midbrain create?

A

A sub-cortical loop that links much of the cerebral cortex with the primary motor and premotor cortices and the brainstem

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5
Q

What is the function of neurons in the subcorticol loop?

Loop created by the components of the basal ganglia

A

Modulate activity in anticipation and during movements

Their effects on upper motor neurons are required for normal performance of voluntary movements

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6
Q

What occurs if the basal ganglia or its associated structures are compromised?

A

The motor system cannot switch smoothly between commands that initiate movement and those that terminate movement

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7
Q

What cortex (es) does the motor loop originate in? (3)

A
  • Primary motor cortex
  • Premotor cortex
  • Supplementary motor cortex
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8
Q

Where does the oculomotor loop originate in? (2)

A
  • Frontal Eye Fields
  • Supplementary Eye Fields
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9
Q

What is the basic pathway (w/out specific structures) for the motor and oculomotor loops)

A

Primary Cortex→Cortical Input→Straitum→Pallidum→Thalamus→Primary Cortex

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10
Q

What is the pathway (including specific structures) for the Oculomotor Loop

A

Striatum→Substantia nigra pars retculata→Superior colliculus

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11
Q

True or False: The Ventral lateral and ventral anterior nuclei (VA/VL complex) is part of the Basal Ganglia

A

FALSE
It is a relay station (thalamus) for the motor loop which sends signals form our principal nuclei back to the cerebral cortex

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12
Q

What are the two parts of the Stratium and what seperates them?

A
  • Caudate
  • Putamen
  • Seperated by the Internal Capsule (myelinated axons leaving and entering the cerebrum)
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13
Q

What region of the basal ganglia has the highest risk of stroke?

A

Striatum

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14
Q

What are the two parts of the Globus Pallidus?

A
  • Internal Segment
  • External Segment
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15
Q

What is the Lenticular Nucleus?

A

The Globus pallidus and Putamen together

Appears as biconvex lens in 3D

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16
Q

What are the parts of the Substantia nigra?

A
  • Pars compacta
  • Pars reticula
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17
Q

What is contained in the Substantia nigra pars compacta?

A

Dopaminergic neurons

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18
Q

All of the following receive output signals from the striatum EXCEPT:

A. Globus pallidus internal segment
B. Substantia nigra pars reticulata
C. Globus pallidus external segment
D. Substantia nigra pars compacta

A

Substantia nigra pars compacta

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19
Q

What is the major recipient of INPUTs to the basal ganglia from the cerebral cortex and midbrain?

A

Straitum

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20
Q

What is the name of the neurons responsilbe for sending output signals from the striatum?

A

Medium Spiny Neurons (MSN)

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21
Q

What location(s) does the MSNs project from the striatum?

A
  • Globus pallidus
  • Substantia nigra pars reticulata
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22
Q

Where does the substantia nigra pars reticulata project into?

A

Superior colliculus

Influences visually guided behavior

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23
Q

What are the two types of MSNs dopamine receptors?

A
  • D1
  • D2
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24
Q

For D1 MSN list the:

  • Neurotransmitter
  • How dopamine is expressed
  • Dendritic pattern
  • “Excitability”
A
  • Neurotransmitter: GABA
  • How dopamine is expressed: Excites
  • Dendritic pattern: More dendrites
  • “Excitability”: Less
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25
Q

For D2 MSN list the:

  • Neurotransmitter
  • How dopamine is expressed
  • Dendritic pattern
  • “Excitability”
A
  • Neurotransmitter: GABA
  • How dopamine is expressed: Inhibits
  • Dendritic pattern: Fewer dendrites
  • “Excitability”: More
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26
Q

What are the OUTPUT pathways of the basal ganglia?

A
  • Direct Pathway
  • Indirect Pathway
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27
Q

What does the DIRECT pathway promote?

A

Promotes movement via disinhibition of the VA/VL thalamus making inputs to cortex more effective

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28
Q

1 of 5

Explain the steps of the DIRECT Pathway

A
  1. Glutamate from the cerebral cortex activates D1 MSN in the striatum.
  2. This triggers the release of GABA onto the globus palidus, internal segment which is tonically active at rest.
  3. GABA from the striatum will thus STOP the release of GABA from the globus palidus, internal segment onto the VA/VL and decrease its inhibition.
  4. Decreased inhibition of the VA/VL complex of the thalamus triggers the release of Glutamate onto the frontal cortex which facilitates movement.
  5. When Dopamine is being released from the substantia nigra pars compacta there will be an excitatory effect on D1 MSN. This will enhance D1 MSN activity and continue to facilitate the direct pathway and movement.
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29
Q

D1 MSNs of the DIRECT pathway facilitates __________ movement

A

Wanted

30
Q

What does the INDIRECT pathway do?

A

Makes direct pathway less effective – VA/VL complex inhibited more.

31
Q

Explain the steps of INDIRECT pathway?

A
  1. Glutamate from the cerebral cortex activates D2 MSN in the striatum.
  2. This triggers the release of GABA onto the globus pallidus, external segment which is tonically active at rest.
  3. GABA from the striatum will thus STOP the release of GABA from the globus pallidus, external segment onto the subthalamic nucleus AND the globus pallidus, internal segment.
  4. Disinhibition of both the subthalamic nucleus and the globus pallidus, internal segment thus increases tonic release of GABA onto the VA/VL complex of the thalamus.
  5. This increases inhibition of the VA/VL complex and prevents Glutamate release onto the frontal cortex. Thus we supress movement.
  6. HOWEVER, when the substantia nigra pars compacta releases Dopamine there is inhibition of D2 MSN and this pathway halts.
32
Q

D1 MSNs of the DIRECT pathway supressed __________ movement

A

Unwanted

33
Q

Cortisol excitation of the STN also ___________ movement

A

Suppresses

34
Q

True or False. The release of Dopamine (regardless of direct or indirect pathway) will lead to movement.

A

TRUE

35
Q

Explain how direct and indirect pathway cooperate

A
  • Direct pathway:Activation of intended movement/motor program
  • Indirect pathway: Suppression of extraneous or inappropriate motor program
36
Q

How did “Optogentic” experiments provide evidence for the two pathways?

A
  • Activation of direct pathway (D1) MSNs reduced freezing and increased locomotion.
  • Bilateral excitation of indirect-pathway (D2) MSNs elicited a “Parkinsonian-like” state by
    increased freezing, bradykinesia, and decreased locomotor initiations.
37
Q

How does Dopamine facilitates movement?

A

By enhancing the direct pathway & moderating (limiting) the indirect pathway via distinct actions on the two types of MSNs

38
Q

What else is found in the striatum that plays a role in modulating behavior?

A

cholinergic (ChAT) striatal interneurons

39
Q

How do Cholinergic interneurons affect the striatum?

A

“Salient stimuli” can trigger the release of Acetylcholine at the striatum

40
Q

What does the release of ACh by cholinergic interneurons lead to?

A
  • Pre-synaptic inhibition of excitatory cortical inputs onto D1 & D2 MSNs
  • Post-synaptic facilitation of the indirect pathway via activation of D2 MSNs
41
Q

How does pre-synaptic inhibiton of D1 and D2 MSNs occur?

A

Inhibition via M2 muscarinic ACh receptors

42
Q

How does post-synaptic inhibition of D2 MSNs occur?

A
  • Activation via M1 muscarinic ACh receptors
  • Receptors not found on D1 MSNs
43
Q

What action can be reflected in dopamine neuron activity?

Low yield

A

Reward “value” of a salient stimulus

44
Q

Explain the Reward “value” of a salient stimulus caused by dopamine neuron activity?

Low yield

A
  • Sensory stimulus serving as a reward elicits a pause response in cholinergic interneurons, in the striatum
  • Simultaneously, burst discharges in dopamine (DA) neurons in the substantia nigra pars compacta
  • The pause in acetylcholine release amplifies the dopamine signal.
45
Q

What does dopamine reniforcement contribute to?

Low yield

A

HABIT formation

46
Q

Explain Habit formation

Low yield

A
  • Habits (mannerisms, customs, and rituals) are largely learned.
  • Habitual behaviors occur repeatedly & can become remarkably fixed.
  • Fully acquired habits are performed almost automatically - allowing attention to be focused elsewhere.
  • Habits tend to involve an ordered, structured action sequence that is prone to being elicited by a particular context
    or stimulus.

Dopamine contributes to the ability to form a habit

47
Q

What is Parkinson’s disease (PD)?

Hypokinetic

A

A chronic progressive neurodegenerative movement disorder caused by degeneration (lost) of dopaminergic inputs to the striatum.

48
Q

List the main motor signs of Parkinson’s Disease (PD)?

“T.R.A.P.”

HIGH yield

A
  • Tremor, or trembling in hands, arms, legs, jaw, or head
  • Rigidity, or stiffness of the limbs and trunk
  • Bradykinesia, or slowness of movement [akinesia - absence, poverty, or loss of control of voluntary muscle
    movements]
  • Postural instability or impaired balance.
49
Q

What other NT is Parkinson’s disease associated with?

A

Norepinephrine (Loss of the nerve endings that produce it)

50
Q

List other signs and symptoms that may accompany Parkinson’s disease

Low yield

A
  • Sleep problems (e.g., REM sleep disorder)
  • Constipation
  • Difficulty with swallowing and chewing
  • Fatigue
  • Depression
  • Emotional changes
  • Skin problems
  • Cognitive problems
  • Orthostatic hypotension
51
Q

How is the excitatory modulation of D1 MSNs diminished d/t Parkinson’s disease?

A
  • There is a DECREASED D1 MSN inhibition of the Globus pallidus internal segment (GPi) in the direct pathway
  • Thus, MORE GPi inhibition of the VA/VL thalamus.
52
Q

How is the inhibitory modulation of MSNs diminshed d/t Parkinson’s disease?

A
  • There is an INCREASED D2 MSN inhibition of the Globus pallidus external segment (GPe)
  • Which causes less GPe inhibition of the STN (and GPi) -> more STN excitation of GPi internal segment
  • Thus, MORE inhibition of VA/VL.
53
Q

What contributes to Hypokinesa (symptom of PD)?

A

The changes in the excitatory D1 MSNs and inhibitory D2 MSNs

54
Q

What does the likelihood of Parkinson’s disease depend on?

A

Genetic factors that increase susceptibility & exposure to environmental factors

55
Q

List the several genes that have been linked of Parkinson’s disease (5)

A
  • Alpha-synuclein (led to the discovery that Lewy Bodies from people with the sporadic form of PD contained clumps of alpha-synuclein protein with a ‘b-pleated sheet’ pattern - “amyloids”)
  • The parkin gene is translated into a protein that normally helps cells break down and recycle proteins.
  • DJ-1 (normally helps regulate gene activity and protect cells from oxidative stress)
  • PINK1 (codes for a protein active in mitochondria. Mutations in this gene appear to increase susceptibility to
    cellular stress)
56
Q

What is the treatment(s) for Parkinson’s disease? (3)

A
  1. Drugs that work directly or indirectly to increase the level of dopamine in the brain (e.g. Levodopa)
  2. Drugs that affect other neurotransmitters in the body in order to ease some of the symptoms of the disease. (e.g. Anticholinergic drugs)
  3. Drugs that help control the non-motor symptoms of the disease (e.g. antidepressants)

Excerise may improve motor control in patients with PD

57
Q

List the basal ganglia loops with predominatly non-motor functions. (2)

A
  • Associative Circuit
  • Limbic Circuit
58
Q

What does the Associative Circuit contribute to?

A

Cognitive tasks referred to as “executive functions”:

  • organizing behavioral responses
  • rule inference
  • conflict management
  • verbal skills in problem
  • working memory
59
Q

What role does the Limbic loop circuit play?

A

A major role in socially appropriate behavior in response to social cues

60
Q

Damage to the Limbic loop circuit is associated to what traits?

A
  • Emotional lability
  • Irritability
  • Failure to respond to social cues
61
Q

What can contribute to mood, personality and behavioral changes in Parkinson’s disease?

A

Changes in the associative and limbic loops

62
Q

What is Huntington’s Disease?

Hyperkinetic

A

Degeneration of MSNs in the indirect pathway (remember - striatum to external GP)

63
Q

List the major signs and symptoms of Huntington’s Disease.

A

Uncontrolled movements in the fingers, feet, face, or trunk

  • Chorea: Uncontrolled, irregular, rapid, jerky movements often occurring with
  • Athetosis: Slow, writhing, involuntary movements of flexion, extension, pronation, and supination of fingers and hands, and sometimes other extremities (toes and feet)
64
Q

What are other issues that arise from Huntington’s?

Low Yield

A
  • Mild clumsiness or problems with balance.
  • Mood swings, irritability, apathy, passivity, depression, or anger
  • HD may also affect the individual’s judgment, memory, and other cognitive functions.
  • Progressive In general, the duration of the illness ranges from 10 to 30 years.
65
Q

What type of disorder is Huntington’s? and how does it happen?

A

Autsomal Dominant Disorder

  • Disease is associated with presence of 40-100 CAG nucleotide repeats on chromosome 4
  • Normal = 6-35 repeats
  • The more repeats you have, the worse symptoms will be
  • Repeats increase with age of disease onset
66
Q

What is the effect of the loss of the stratium b/c of Huntington’s dieases?

A
  • Leads to DECREASED inhibition of the globus pallidus.
  • This will INCREASE the tonic release of GABA from the globus pallidus onto the subthalamic nucleus and VA/VL
  • Leading to increased excitation of the frontal cortex.
67
Q

Which of the following correctly describes the effects of glutamatergic signaling (from the cerebral cortex) on D1 MSN’s?

A. ↑ inhibition of Globus pallidus internal segment; ↓ inhibition of VA/VL complex
B. ↓ inhibition of Globus pallidus external segment; ↑ inhibition of VA/VL complex
C. ↓ inhibition of Globus pallidus internal segment; ↑ inhibition of VA/VL complex
D. ↑ inhibition of Globus pallidus external segment; ↓ inhibition of VA/VL complex

A

A. ↑ inhibition of Globus pallidus internal segment; ↓ inhibition of VA/VL complex

68
Q

Scientists at the Morsani College of Medicine are studying a rare congenital defect which leads to excess production and release of acetylcholine within the basal ganglia. Which of the following symptoms would a patient suffering from this condition likely experience?

A. Athetosis
B. Motor impulsivity
C. Bradykinesia
D. Chorea

A

c. Bradykinesia

69
Q

Parkinson’s Disease is characterized by the loss of dopaminergic neuronal cells in the substantia nigra and abnormal accumulation of Lewy bodies within the brain. What protein is responsible for Lewy body aggregation?

A. Parkin
B. α-synuclein
C. DJ-1
D. PINK1

A

α-synuclein

70
Q

Huntington’s disease is a rare, congenital disorder that causes the progressive degeneration of structures responsible for voluntary movement. Which of the following correctly describes the pathology of this condition?

A. ↑ inhibition of Subthalamic nucleus; ↑ inhibition of VA/VL complex
B. ↓ inhibition of Globus pallidus external segment; ↑ inhibition of VA/VL complex
C. ↑ inhibition of Globus pallidus internal segment; ↓ inhibition of VA/VL complex
D. ↓ inhibition of Subthalamic nucleus; ↓ inhibition of VA/VL complex

A

c. ↑ inhibition of Globus pallidus internal segment; ↓ inhibition of VA/VL complex

71
Q

Dr. Yao’s sample question

The medium spiny neurons of the striatum have which of the following characteristics?

A. Are excitatory and release dopamine
B. Are excitatory and release glutamate
C. Are inhibitory and release GABA
D. Are inhibitory and release dopamine

A

Are inhibitory and release GABA

72
Q

Dr. Yao’s in class sample question

The EMG (electromyography) directly measures of the electrical activity of:

A. Only alpha motor neurons
B. Only gamma motor neurons
C. Motor units
D. Muscle spindel afferents

A

Motor units

Measures muscle activity

Neuroscience Exam 2 (9 decks)

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