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Exam 2 APP > APP Module (GTown) - Basal Ganglia Pathophysiology (Hrs 1 and 2) > Flashcards

APP Module (GTown) - Basal Ganglia Pathophysiology (Hrs 1 and 2) Flashcards

1
Q

What is the generalized function of the basal ganglia?

A

the selection of action, or turning thoughts/ideas/motivations into action

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2
Q

What are the key pathologies of the basal ganglia?

A

1) Parkinson’s Disease
2) Huntington Disease
3) Tourette’s
4) dementia pugilistica
5) OCD

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3
Q

What is the main motor circuit called which includes the basal ganglia?

A

cortico-basal ganglia-thalamocortical circuit

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4
Q

What are the two brain areas of the dorsal striatum?

A

caudate and putamen

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5
Q

What separates the caudate and putamen?

A

internal capsule

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6
Q

What are the majority of neurons in the basal ganglia?

A

medium spiny neurons (MSNs)

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7
Q

What are the two motor pathways in the basal ganglia?

A

The direct and indirect pathways

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8
Q

What type of input does the basal ganglia get from the cortex?

A

mostly excitatory glutamatergic input

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9
Q

What type of input does the basal ganglia get from the substantia nigra?

A

both excitatory and inhibitory dopaminergic input

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10
Q

What is the role of the subthalamic nucleus?

A

suppression of unwanted movements

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11
Q

How do you differentiate between the two types of dopaminergic neurons which originate from the substantia nigra pars compacta and synapse on the dorsal striatum?

A

D1-like neurons will project to the substantia nigra pars reticulata. D2-like neurons will project to the globus pallidus externa.

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12
Q

What are the two neural components of the basal ganglia?

A

1) Principal, projecting neurons (~95%)

2) Aspiny interneurons (1-2%)

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13
Q

What neurotransmitters do the interneurons use?

A

GABA and acetylcholine

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14
Q

What do the interneurons in the basal ganglia do?

A

Modulate MSNs

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15
Q

What electrophysiological properties do the MSNs have?

A

bimodal nature: up and down states

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16
Q

What is the purpose of the MSNs?

A

to convey information out of the basal ganglia

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17
Q

What are the three main inputs onto the average MSN?

A

1) cortical glutamatergic input
2) interneuronal ACh input
3) substantia nigra DA input

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18
Q

What are the four cortical-basal ganglia loops?

A

1) motor
2) oculomotor
3) prefrontal
4) limbic

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19
Q

What are the main inputs into the striatum?

A

Dorsal striatum

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20
Q

What NT do neurons in the globus pallidus use?

A

GABA

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21
Q

Where do the majority of neurons from the GP synapse on?

A

Thalamus

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22
Q

How long does it take for a signal to cross a synapse?

A

2 ms

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23
Q

How do we know there is an indirect GABA influence on the basal ganglia?

A

There is a 20-30 ms lag between stimulation of the cortex and a spike in the basal ganglia.

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24
Q

Where do the majority of neurons from the STN project to?

A

GP

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25
Q

What NT does the STN use?

A

glutamate

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26
Q

Why is the STN unique in the BG?

A

It is the only brain region to use glutamate

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27
Q

What are the two subdivisions of the substantia nigra?

A

pars compacta and pars reticulata

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28
Q

What neuromodulator does the SN use?

A

dopamine

29
Q

What regulates the firing patterns in the SN?

A

salience

30
Q

What are the two types of GABA neurotransmission and what type of channels are they?

A

GABA-A (metabotropic)

GABA-B (ionotropic)

31
Q

What are the two types of glutamatergic channels?

A

1) metabotropic (mGlu)

2) ionotropic (AMPA, NMDA, and kainate)

32
Q

What type of channels are attached to NMDA receptors?

A

non-selective cation channels

33
Q

What are the two major types of dopaminergic receptors?

A

1) D1-like

2) D2-like

34
Q

What types of receptors are DAergic receptors?

A

GPCRs

35
Q

What is the effect of D2R activation?

A

↓ [cAMP], ↑ K channels, ↓ Ca channels

36
Q

What is the effect of D1R activation?

A

↑ [cAMP], ↑ [Ca]

37
Q

What NT do tonically active neurons use?

A

acetylcholine

38
Q

What are some clinical aspects of basal ganglia pathophysiology?

A
  • tremor
  • changes in posture and muscle tone
  • poverty of movement
  • shuffling gait with bending at the waist
  • hyperkinetic involuntary movements
  • obsessive-compulsive disorders
39
Q

What is the theory of Parkinsonism?

A

unbalance activity of the direct and indirect pathway underlies development of PD

40
Q

What is the neuroanatomical correlate of PD?

A

progressive death of DA cells of the substantia nigra in the midbrain

41
Q

What are the features of Parkinsonism?

A
  • resting tremor
  • poor postural balance
  • bradykinesia
  • muscle rigidity
42
Q

What are some demographics of PD diagnosis?

A
  • usually occurs in late middle age
  • both sexes affected equally
  • Caucasians are affected more than Asians and Africans
  • there is some genetic correlation
43
Q

What is MPTP?

A

A meperidine derivative that causes Parkinson-like symptoms and can be used for animal models of PD

44
Q

What are the effects on the basal ganglia motor pathways in PD?

A

increased activity in the indirect pathway

decreased activity in the direct pathway

45
Q

What amount of cases in PD are sporadic?

A

> 95%

46
Q

What is another exogenous cause of PD?

A

chronic pesticide exposure

47
Q

What is the mainstay of treatment for PD?

A

levodopa

48
Q

What is L-dopa?

A

precursor to dopamine which can cross the BBB

49
Q

What is a side effect of taking L-dopa?

A

dyskinesia over time

50
Q

What is L-dopa co-administered with and why?

A

coadministered with an AAD inhibitor so it is not converted to dopamine in the periphery

51
Q

What are some dopamine receptor agonists used for PD?

A

bromocriptine, pergolide

52
Q

What are some MAO-B inhibitors used for treatment of PD?

A

selegiline, rasagiline

53
Q

What are the two main surgical therapies for PD?

A

1) ablation, usually unilaterally of the globus pallidus

2) deep brain stimulation of the STN/GP bilaterally

54
Q

What is the neuroanatomical correlate for Huntington’s disease?

A

unique loss of the striatal projection neurons

55
Q

Which pathway is affected more in HD?

A

indirect pathway

56
Q

What are some of the motor movements seen in HD?

A
  • grimacing of the face
  • twitching
  • gesticulating with the arms
  • jerking
57
Q

What genetic defect underlies HD?

A

expansion of DNA repeats in gene that produces huntingtin protein

58
Q

What is treatment for HD?

A

usually no medication for the disease per se, but rather the associated depression, paranoia, irritability

59
Q

What is hemiballismus?

A

hyperkinetic movement disorder, more severe than HD which effects one half of the body (or one extremity)

60
Q

What is hemiballismus caused by?

A

unilateral lesion of the STN

61
Q

What does hemiballismus cause in the basal ganglia motor pathway?

A

Decreased levels of GP output

62
Q

What is Tourette’s characterized by and when is it usually diagnosed?

A

motor and vocal tics and is usually diagnosed in childhood

63
Q

What do Tourette’s patients have an increased comorbidity for?

A
  • OCD
  • ADHD
  • depression
64
Q

What is the underlying neurological cause of Tourette’s?

A

hyperdopaminergic tone

65
Q

What are some pharmacological therapies for Tourette’s?

A

Dopamine antagonists like haldol and risperdal

66
Q

What are the disorders which are obsessive-compulsive nature characterized by in the brain?

A

dysfunctional limbic system also involving the basal ganglia

67
Q

What seems to be the underlying brain region in addiction?

A

ventral striatum

68
Q

What does all addictions share in common?

A

increased dopamine in the ventral striatum

Exam 2 APP (5 decks)

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