4 Basal Ganglia And Motor Control - Leonard

Front 1

In general, what do lesions in the basal ganglia result in?

Back 1

1. movement disorders
2. May also cause significant impairment in cognitive and perceptual functions and mentations

Front 2

How are the basal ganglia organized?

Back 2

Anatomically and functionally in parallel circuits

Front 3

T/F - the basal ganglia operate primarily by disinhibition?

Back 3

True - excitatory effects are achieved by removal of synaptic inhibition rather than by increasing synaptic excitation

Front 4

In general, how are diseases of the basal ganglia characterized?

Back 4

Disruption of neurochemical interactions/transmission -- not all diseases result from the loss of a single NT, but rather specific neurochemical disruptions do occur in all diseases.

Front 5

The basal ganglia consists of what 5 interconnected subcortical nuclei?

Back 5

1. caudate n.
2. putamen
3. globus pallidus
4. subthalamic n.
5. substantia nigra

Front 6

From what embryological structure does the caudate and putamen form?
Are these the major input or output to the basal ganglia?

Back 6

1. telecephalon
2. input

Front 7

What is the major neuron in the caudate and putamen, and what is the main NT?

Back 7

1. medium spiny neuron
2. GABA

Front 8

From what embryological structure does the globus pallidus form?
What's the main NT used?

Back 8

1. diencephalon
2. GABA

Front 9

From what embryological structure does the subthalamic n. form?
What NT is used and what is unique about this?

Back 9

1. diencephalon
2. glutamate -- it is the only excitatory nucleus in the basal ganglia

Front 10

In what part of the brain is the substantia nigra located?
Whats the major NTs of the pars reticulata and the pars compacta?

Back 10

1. midbrain
2. reticulata --> GABA
3. compacta --> dopamine

Front 11

The most important input to the basal ganglia comes from the ____ and virtually all the axons terminate in the _____?

Back 11

1. cortex
2. striatum

Front 12

From where in the cerebral cortex does the basal ganglia receive input?

Back 12

Everywhere -- including motor, sensory, association, and limbic areas

Front 13

Is the input to the basal ganglia topographically organized?

Back 13

YES

Front 14

What are the inputs to the putamen mainly involved with?

Back 14

motor control

Front 15

What are the inputs to the caudate mainly involved with?

Back 15

1. eye movements
2. cognitive function

Front 16

What are the inputs to the ventral striatum (n. accumbens) mainly involved with?

Back 16

limbic functions

Front 17

What is the function of the Direct Pathway?

Back 17

Aids in cortically activated movement execution (facilitates the flow of information through the thalamus by disinhibition)

Front 18

Name the steps in the direct pathway.

Back 18

Cortex --> (+) putamen --> (-) globus pallidus interna --> (-) thalamus --> (+) cortex

Front 19

What is the function of the Indirect Pathway?

Back 19

Prevents unintended movements (inhibits the flow of information through the thalamus, also by disinhibition)

Front 20

Name the steps in the indirect pathway.

Back 20

Cortex --> (+) putamen --> (-) globus pallidus externa --> (-) subthalamic n. --> (+) globus pallidus interna --> (-) thalamus --> (+) cortex

Front 21

What are the NTs of the striatum?

Back 21

1. GABA / Substance P in the DIRECT pathway

2. GABA / Enkephalin in the INDIRECT pathway

Front 22

What is the key integration point in both direct and indirect pathways?

Back 22

The GPi (firing decreases in direct pathway and increases in indirect pathway)

Front 23

What is the role of the substantia nigra in the direct and indirect pathways?

Back 23

the SNpc projects dopamine to the striatum to modulate both pathways, ultimately by promoting movement.

Front 24

How does the SNpc promote movement in both direct and indirect pathways?

Back 24

1. Direct - SNpc --> (+) striatum via D1 receptors

2. Indirect - SNpc --> (-) striatum via D2 receptors

Front 25

Disorders/lesions of the basal ganglia lead to what types of signs?

Back 25

1. hyperkinetic (positive) signs; results from enhanced direct pathway and diminished indirect

2. hypokinetic (negative) signs; results from enhanced indirect pathway and diminished direct

Front 26

Are negative signs in diseases of the basal ganglia a result of muscle weakness?

Back 26

No -- it's due to loss of normal control, e.g. poor reduction in tension by antagonist muscles --> leads to rigidity

Front 27

Name two examples of hypokinetic disturbances

Back 27

1. bradykinesia - slow movement
2. akinesia - impairment of the initiation of movement

Front 28

Name three examples of hyperkinetic disturbances

Back 28

1. ballism - uncontrolled flinging of upper and lower extremities

2. choreiform movements - involuntary "dance-like" spasmodic movements of the limbs

3. athetoid movements - writhing or snake-like movements of the distal extremities

Front 29

What will a lesion in the neostriatum (caudate + putamen) result in?

Back 29

hypokinetic disturbance; primary affects direct pathway; GPi fires more and causes thalamus to fire less

Front 30

What will a lesion in the subthalamic n. on one side result in?

Back 30

hemiballism; primarily affects indirect pathway; GPi fires less and causes thalamus fires more

Front 31

What does Parkinson's disease lead to by affecting the direct/indirect pathways?

How are firing patterns in direct/indirect pathways affected?

Back 31

1. hypokinesis
2. profound loss of DA reduces firing in direct pathway and reduces inhibition in indirect pathway

Front 32

What are symptoms in Parkinson's disease?

Back 32

1. akinesia
2. bradykinesia
3. rigidity
4. pill-rolling tremor (resting tremor)
5. paucity of movement
6. shuffled gait and flexed posture
7. masked face (reptilian stare)

Front 33

What is the mainstay treatment of Parkinson's disease?

Back 33

L-DOPA (can cross the BBB) + Carbidopa (inhibits peripheral DA synthesis)

Front 34

What designer drug contaminant is metabolized into a toxic compound causing a Parkinson-like syndrome?

Back 34

MPTP - a meperidine analog
(1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)

Front 35

What does Huntington's disease lead to by affecting the direct/indirect pathways? Which pathway is initially affected?

What's the genetic inheritance pattern?

Back 35

1. Absent mindedness, irritability, clumsiness, and falls in the early stages
2. Hyperkinesis gradually begins (e.g. chorea)
--> seems to target the indirect pathway initially

3. Autosomal dominance of CAG repeats.

Front 36

What basal ganglia structure is affected in Huntington's disease? What NTs are lost because of this?

Back 36

Striatum (primarily the caudate) that results in loss of ACh and GABA

Front 37

What is the age on onset for Huntington's? What is the prognosis?

Back 37

1. Late onset - usually in 30s-40s

2. Pts show increasing dementia and die within 15-20 years after onset.

Front 38

What chromosome has been identified as a possible cause for the degeneration of neurons in Huntington's?

Back 38

Mutation on chromosome 4; may be related to excitotoxicity

Front 39

Name three similarities between basal ganglia and cerebellar function

Back 39

1. both form major subcortical loops that control movement
2. both receive major inputs from the cortex
3. both project back to the cortex via the thalamus

Front 40

Name 3 important differences between basal ganglia and cerebellar function.

What do these differences suggest?

Back 40

1. BG receives input from entire cortex; CB only from sensory/motor corticies

2. CB output is direct to the premotor and motor corticies while the BG also projects to the prefrontal association cortex

3. CB receives somatic sensory info directly from the spinal cord and has many afferent/efferent connections with brainstem nuclei. The BG has few connections to the brainstem and no connections directly to the spinal cord.

--> the CB is directly involved in execution of movement while the BG are involved with higher-order and cognitive aspects of movement (e.g. planning and execution of complex motor strategies). The BG also has limbic associations which suggests that it is involved with many other non-motor control functions, unlike the CB.

Front 41

What motor function is the dentate nucleus primarily responsible for?
Interpositus?
Fastigial?

Back 41

Dentate --> motor planning
Interpositus --> motor execution
Fastigial --> Balance and eye movement

Front 42

What do lesions of the cerebellum cause?

Back 42

1. hypotonia (low muscle tone)
2. ataxia (uncoordinated walking)
3. dysmetria (an aspect of ataxia, in which the ability to control the distance, power, and speed of an act is impaired)
4. dysdiadochokinesis (difficulty making rapid alternating movements)
5. intention tremor (occurs during the performance of precise voluntary movements)

Front 43

Cooling the deep cerebellar nuclei (mainly the interposed n.) leads to what?

Back 43

Oscillating limb movements resulting from lack of cerebellar coordination of opposing muscles. In general, limb instability results.
--> CB is important for how long stretch reflexes are engaged

Front 44

How does the movement disorders in cerebellar disease compare to Parkinson's disease?

Back 44

In a reaching motion, CB disease has longer latency and good ballistic movement, but the end position cannot be maintained

In Parkinson's, there is a delayed onset of movement and ballistic movement is slow (suggesting a problem in feed-forward control). However, the end position is stable once they get there.

Front 45

How does the cerebellum participate in higher-order functions?

Back 45

1. activity in the dentate is significantly greater when the patient is mentally/cognitively active during movement

2. the CB also participates in motor learning