09 09 2014 Basal Ganglion

Question 1

What is the basal Ganglia

Answer 1

cluster of nuclei in the cerebrum, diencephalon, and midbrain that function together to facilitate or inhibit behaviors and actions.

-play large role in movement (also play a role in emotion and cognition and eye movement)

Question 2

Basal Ganglia loops

• loop?
• What does it help in?

Answer 2

Cortex-Cortex

• -Motor cortex sends signal to striatum.
• Striatum sends output to Globus pallidus.
• Internal Globus pallidus sends signal to VA/VL
• VA/VL (thalamus) sends signal back to cortex

Facilitates motor cortical areas – turns up excitability

1. initiates movement
2. sequencing movement
3. automaticity

Question 3

What happens when there is a lesion in the basal ganglia

Answer 3

Increase or decrease in movement

Question 4

Dopamine modulates actions in the basal ganglia, limbic system and prefrontal cortex through which pathways?

Answer 4

1. Nigrostriatal pathway (aka mesostriatal) – dopaminergic neurons that control of movements. Projects to caudate and putamen. Defect = parkinson’s disease ( Basal ganglia)
2. Mesolimbic pathwy – dopminergic neurons that regulate the reward pathway. Defects = schizophrenia (positive symptoms) and/or depression
   (Limbic system)
3. Mesocortical pathway- working memory. Defects may play a role in Schizophrenia (negative symptoms), hypokinesia seen in Parkinson’s.

Question 5

Mechanisms of VA/VL

Answer 5

Excites motor complex by increasing motor output

-Glutamate

Question 6

Internal Global Pallidus

Answer 6

provides tonic inhibition to VA/VL

-GABA

Question 7

Disinhibition vs. Excitation

Answer 7

Disinhibition: inhibition of internal globes pallid us cause more excitation of VA/VL to cortex

Excitation: Internal Globus Pallidus gets excited via input. It leads to more inhibition of VA/VL –> less signals sent to motor cortex

Question 8

Who excites GPi and who inhibits GPi?

Answer 8

• Subthalamic nucleus excites GPi – causing inhibition of cortex and movement
• Striatum inhibits GPi – causing more excitation of cortex and movement.

Question 9

What would happen to the frequency of movement if there was a lesion in the sub thalamic nucleus?

Answer 9

produce too much movement (contralateral hemiballismus – wild flinging movement)

-Subthalamic nucleus excites GPi – causes damping of VA/VL and cortex signals.

Question 10

Direct pathway (loop)

Answer 10

Facilitiates movement

-disinhibition of GPi (from striatum) that increases activation of VA/VL

Question 11

Indirect pathway (loop)

Answer 11

Inhibits unwanted movement

-disinhibition of subthalamic nucleus – increases GPi = decrease VA/VL signaling

Question 12

The effect of dopamine to both the direct and indirect pathway ( general)

Answer 12

Dopamine facilities movement! Increase signaling from VA/VL to motor cortex

Question 13

How/ what is the mechanism by which dopamine increases signaling to motor cortex (via VA/VL) via direct ?

Answer 13

• dopamine from substance nigra pars compactus binds to DA1 receptors in Striatum (excitatory). They inhibit GPi (downstream)

Question 14

How/ what is the mechanism by which dopamine increases signaling to motor cortex (via VA/VL) via the indirect pathway?

Answer 14

Dopamine neurons from substance nigra target D2 receptors (inhibitory) on striatum (putamen) . Inhibits sub thalamic nucleus which therefore also inhibits GPi stimulation.

Releases VA/VL from inhibition

Question 15

Acetylcholine is present in the striatum. In what pathway does it have an effect and what is the effect?

Answer 15

ACh is in striatum and is most effective in indirect pathway.

It excites the indirect pathway –> tends to inhibit movement.

Anticholinergics are effective if you want more movement in Parkinson’s disease

Question 16

hypokinesia

Answer 16

too little movement

“negative symptoms”

Question 17

Hyperkinesia

Answer 17

too much movement

“positive symptoms”

Question 18

Dyskinesia

Answer 18

abnormal movement

Question 19

If there is a lesion in basal ganglia, where will the effects be seen– ipsilateral or contralateral?

Answer 19

contralateral

• basal ganglia is sitting right next to motor complex.
• -regulates pathway on same side so of course it affects the opposite side of the body.

Question 20

Negative symptoms of Basal Ganglia disease

Answer 20

Parkinson’s disease

• Akinesia (no movement)
• Bradykinesia (slow movement)
• Decreased postural adjustments
• Hypokinesai (decreased amplitude of movements
  - handwriting gets smaller

Question 21

Positive symptoms of Basal Ganglia disease

Answer 21

-rigidity

• dystonia-increased muscle tone in isolated muscles
  - limbs to bend/twist
  - head turned to one side (CN 11)
• athetosis: slow, writhe ring movements in lips, hands, and fingers. Patients cannot maintain fixed position.
• chorea: continuous rapid movements of face, tonuge, and limbs. Most common with Huntingont’s
• Hemiballismus – violent, involuntary flailing movements
• Tics
• Tardive dyskinesia : from antipsychotic or antiemetic drugs- causes dyskinesia
• Tremor–
• Prakinson’s: 3-5 hz at rest: hands and arms. beginning unilaterally.
• Essential tremor:5-8 Hz : everywhere. Usually bilaterally.– basal ganglia

-Myoclonus: sudden rapid muscular jerks – whole body. damage = basal ganglia, cerebellum and cortex.

Question 22

what are the 4 parallel basal ganglia pathways

Answer 22

1. motor
2. Oculomotor – abnormal eye movements
3. Cognition (prefrontal)
4. Emotions (limbic)

Question 23

What are two diseases that result from damage to basal ganglia

Answer 23

1. Huntington’s Chorea

2. Parkinson’s disease

Question 24

Huntington’s Chorea

what is it?
onset?
Prognosis?
Treatment?

Answer 24

Autosomal dominant neurodegenerative disorder with cell loss in caudate and putamen.

onset = 40s-50s

progressive and degenerative

Median survival = 15 years

treated with drugs that decrease dopamine.

Question 25

Major symptoms with huntington's chorea

Answer 25

1. chorea: rapid movements of face, tongue, limbs. 2. dementia (cognitive impairment) 3. psychiatric manifestations - anxiety - moodiness - OCD - Impulsiveness

Question 26

What basal ganglia pathway does Huntington's disease affect?

Answer 26

Indirect pathway -cell death of caudate and putamen causes loss of inhibition of sub thalamus. Subthalamus is inhibited so stimulation of GPi is lost. VA/VL is released from inhibition = increase in movement

Question 27

Cardinal symptoms of PD

Answer 27

BEGIN UNILATERALLY - Bradykinesia - resting tumor (pill rolling motion) - rigidity - postural instibilty

Question 28

Other motor symptoms of parkinson's

Answer 28

- Masked facies (hypomimia)-- no emotional feeback. - Festination gait -- a shuffle that starts out slowly and then increases in speed. - stooped posture - freezing - difficulty turing in bed.

Question 29

What are some non-motor symptoms?

Answer 29

symptoms can spread across systems. May develop dementias and other cognitive/behavioral disorders

Question 30

what are some treatment options of PD

Answer 30

1. pharmaceutical (look at pharm lecture for PD) 2. Surgical lesions - Thalamus : young unilateral tremor and no rigidity or bradykinesai. - Globus pallidus (internal) for tremor and rigidity 3. Deep-brain stimulation - GPi - Subthalamic nucleus - Thalamus.

Question 31

How does deep brain stimulation work?

Answer 31

1. normalizes outputs | 2. blocks action potential

Question 32

What is the more common neuroprotective treatment?

Answer 32

Exercise -neuroprotective AND neurorestorative (after lesions)

Question 33

Parkinson's plus syndromes

Answer 33

1. lack of resting tremor 2. symmetrical symptoms 3. Early postural instability 4. Lack of response to dopamine 5. Progressive supranuclear palsy-- above CN nuclei. Affects rostral brain.