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

Question 1

What is the generalized function of the basal ganglia?

Answer 1

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

Question 2

What are the key pathologies of the basal ganglia?

Answer 2

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

Question 3

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

Answer 3

cortico-basal ganglia-thalamocortical circuit

Question 4

What are the two brain areas of the dorsal striatum?

Answer 4

caudate and putamen

Question 5

What separates the caudate and putamen?

Answer 5

internal capsule

Question 6

What are the majority of neurons in the basal ganglia?

Answer 6

medium spiny neurons (MSNs)

Question 7

What are the two motor pathways in the basal ganglia?

Answer 7

The direct and indirect pathways

Question 8

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

Answer 8

mostly excitatory glutamatergic input

Question 9

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

Answer 9

both excitatory and inhibitory dopaminergic input

Question 10

What is the role of the subthalamic nucleus?

Answer 10

suppression of unwanted movements

Question 11

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?

Answer 11

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

Question 12

What are the two neural components of the basal ganglia?

Answer 12

1) Principal, projecting neurons (~95%)

2) Aspiny interneurons (1-2%)

Question 13

What neurotransmitters do the interneurons use?

Answer 13

GABA and acetylcholine

Question 14

What do the interneurons in the basal ganglia do?

Answer 14

Modulate MSNs

Question 15

What electrophysiological properties do the MSNs have?

Answer 15

bimodal nature: up and down states

Question 16

What is the purpose of the MSNs?

Answer 16

to convey information out of the basal ganglia

Question 17

What are the three main inputs onto the average MSN?

Answer 17

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

Question 18

What are the four cortical-basal ganglia loops?

Answer 18

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

Question 19

What are the main inputs into the striatum?

Answer 19

Dorsal striatum

Question 20

What NT do neurons in the globus pallidus use?

Answer 20

GABA

Question 21

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

Answer 21

Thalamus

Question 22

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

Answer 22

2 ms

Question 23

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

Answer 23

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

Question 24

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

Answer 24

GP

Question 25

What NT does the STN use?

Answer 25

glutamate

Question 26

Why is the STN unique in the BG?

Answer 26

It is the only brain region to use glutamate

Question 27

What are the two subdivisions of the substantia nigra?

Answer 27

pars compacta and pars reticulata

Question 28

What neuromodulator does the SN use?

Answer 28

dopamine

Question 29

What regulates the firing patterns in the SN?

Answer 29

salience

Question 30

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

Answer 30

GABA-A (metabotropic) | GABA-B (ionotropic)

Question 31

What are the two types of glutamatergic channels?

Answer 31

1) metabotropic (mGlu) | 2) ionotropic (AMPA, NMDA, and kainate)

Question 32

What type of channels are attached to NMDA receptors?

Answer 32

non-selective cation channels

Question 33

What are the two major types of dopaminergic receptors?

Answer 33

1) D1-like | 2) D2-like

Question 34

What types of receptors are DAergic receptors?

Answer 34

GPCRs

Question 35

What is the effect of D2R activation?

Answer 35

↓ [cAMP], ↑ K channels, ↓ Ca channels

Question 36

What is the effect of D1R activation?

Answer 36

↑ [cAMP], ↑ [Ca]

Question 37

What NT do tonically active neurons use?

Answer 37

acetylcholine

Question 38

What are some clinical aspects of basal ganglia pathophysiology?

Answer 38

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

Question 39

What is the theory of Parkinsonism?

Answer 39

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

Question 40

What is the neuroanatomical correlate of PD?

Answer 40

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

Question 41

What are the features of Parkinsonism?

Answer 41

- resting tremor - poor postural balance - bradykinesia - muscle rigidity

Question 42

What are some demographics of PD diagnosis?

Answer 42

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

Question 43

What is MPTP?

Answer 43

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

Question 44

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

Answer 44

increased activity in the indirect pathway | decreased activity in the direct pathway

Question 45

What amount of cases in PD are sporadic?

Answer 45

>95%

Question 46

What is another exogenous cause of PD?

Answer 46

chronic pesticide exposure

Question 47

What is the mainstay of treatment for PD?

Answer 47

levodopa

Question 48

What is L-dopa?

Answer 48

precursor to dopamine which can cross the BBB

Question 49

What is a side effect of taking L-dopa?

Answer 49

dyskinesia over time

Question 50

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

Answer 50

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

Question 51

What are some dopamine receptor agonists used for PD?

Answer 51

bromocriptine, pergolide

Question 52

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

Answer 52

selegiline, rasagiline

Question 53

What are the two main surgical therapies for PD?

Answer 53

1) ablation, usually unilaterally of the globus pallidus | 2) deep brain stimulation of the STN/GP bilaterally

Question 54

What is the neuroanatomical correlate for Huntington's disease?

Answer 54

unique loss of the striatal projection neurons

Question 55

Which pathway is affected more in HD?

Answer 55

indirect pathway

Question 56

What are some of the motor movements seen in HD?

Answer 56

- grimacing of the face - twitching - gesticulating with the arms - jerking

Question 57

What genetic defect underlies HD?

Answer 57

expansion of DNA repeats in gene that produces huntingtin protein

Question 58

What is treatment for HD?

Answer 58

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

Question 59

What is hemiballismus?

Answer 59

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

Question 60

What is hemiballismus caused by?

Answer 60

unilateral lesion of the STN

Question 61

What does hemiballismus cause in the basal ganglia motor pathway?

Answer 61

Decreased levels of GP output

Question 62

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

Answer 62

motor and vocal tics and is usually diagnosed in childhood

Question 63

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

Answer 63

- OCD - ADHD - depression

Question 64

What is the underlying neurological cause of Tourette's?

Answer 64

hyperdopaminergic tone

Question 65

What are some pharmacological therapies for Tourette's?

Answer 65

Dopamine antagonists like haldol and risperdal

Question 66

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

Answer 66

dysfunctional limbic system also involving the basal ganglia

Question 67

What seems to be the underlying brain region in addiction?

Answer 67

ventral striatum

Question 68

What does all addictions share in common?

Answer 68

increased dopamine in the ventral striatum