3: Basal Ganglia Flashcards

1
Q

What is the general function of the basal ganglia? (2)

A

Planning and initiating movement

Regulating muscle tone and posture

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2
Q

Four broad generalities about the basal ganglia:

  • -Where does most input come from?
  • -Where does most output go to?
  • -How does the basal ganglia modulate cortical activity?
  • -What results form damage to the basal ganglia?
A

Input from CEREBRAL CORTEX
Output back to CEREBRAL CORTEX topographically
Modulation: intrinsic circuits and NT systems, esp. dopamine
Damage -> disorders of movement, also damage to other cortical functions

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3
Q

(OBJ) List the anatomical components of the extrapyramidal system (3 major components, 5 subdivisions).

A

Extrapyramidal system:

  1. Basal ganglia
    - -Caudate and putamen nuclei (striatum)
    - -Globus pallidus (with lateral and medial divisions)
  2. Substantia nigra of midbrain
    - -Pars reticulata
    - -Pars compacta
  3. Subthalamic nucleus
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4
Q

(OBJ) Describe the relative locations of the anatomical components of the extrapyramidal system: basal ganglia (caudate, putamen, globus pallidus), substantia nigra (pars reticulata and pars compacta), and the subthalamic nucleus.

A

Basal ganglia:

  • -Caudate located on lateral wall of lateral ventricle
  • —Long body and tail, extending from the putamen
  • -Putamen lateral, separated from caudate by internal capsule
  • —Putamen = body of tadpole, caudate = tail of tadpole, merged anteriorly (nucleus accumbens), then extending medially and superior, then inferior to putamen
  • -Globus pallidus located directly lateral to thalamus (separated by internal capsule) and immediately medial to putamen
  • —Has lateral (external) and medial (internal) divisions

Substantia nigra located in rostral midbrain

Subthalamic nucleus in caudal diencephalon, ventral to thalamus

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5
Q

Very briefly, what is the claustrum? (2)

A

A Y-shaped gray matter tract located between the putamen and the insular cortex
Possibly helps modulate rhythmic cortical activity

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6
Q

(OBJ) Diagram the direct pathway for information transmission through the basal ganglia and discuss its physiological role.

A

DIRECT = FACILITATING movement and cortical excitability
–Terminates narrowly, facilitates only those motor programs that are appropriate

  1. Cerebral cortex -> excitatory input to caudate/putamen
    - -Substantia nigra pars compacta also -> caudate/putamen through D1 dopamine receptors
  2. Caudate/putamen inhibit tonically active/inhibitory neurons of INTERNAL segment of globus pallidus
  3. Disinhibition of VA/VL of thalamus by globus pallidus -> activation of VA/VL
  4. VA/VL -> excitatory thalamic feedback to frontal cortex

[SUMMARY: cortex/SN -!-> C/P -x-> IS of GP -x!x-> VA/VL -!-> cortex]

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7
Q

What is disinhibition?

A

Inhibition of an inhibitory part of a circuit

Net result = facilitation

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8
Q

(OBJ) Diagram the indirect pathway for information transmission through the basal ganglia and discuss its physiological role.

A

INDIRECT = INHIBITING movement and cortical excitability
–Terminates broadly, provides an inhibitory background

  1. Cerebral cortex -> excitatory input to caudate/putamen
    - -Substantia nigra pars compacta INHIBITS caudate/putamen through D2 dopamine receptors (OPPOSITE)
  2. Caudate/putamen inhibit tonically active/inhibitory neurons of EXTERNAL segment of globus pallidus
  3. Disinhibition of subthalamic nucleus by globus pallidus -> excitement of subthalamic nucleus
  4. Subthalamic nucleus -> excitatory input to internal segment of globus pallidus -> inhibition of VA/VL

[SUMMARY: cortex -!-> C/P -x-> ES of GP -x!x-> subthalamic nucleus -!-> IS of GP -x-> VA/VL -x-> cortex]

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9
Q

(OBJ) Explain the effects of dopamine in the striatum and the implications of excess or deficiency of dopamine transmission.

A

Inhibits indirect pathway, facilitates direct pathway -> facilitates cortical activity

  • -Loss of dopamine = inhibitory; difficulty initiating movements, slowness in performance of movements
  • -Excess dopamine = excitatory; too much movement
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10
Q

What are the only two areas that do not make input to the striatum?

A

Primary visual and primary auditory cortices

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11
Q

Briefly, describe evidence for segregation of circuits within the basal ganglia.

A

Segregation: parallel circuits feedback to specific, functionally distinct areas of cortex

  • -Mapping motor, premotor, supplementary motor cortices onto putamen, GP, SN, and VA/VL -> very specific/targeted regions on each
  • -Each area feeds back to the same cortical region that gave it input
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12
Q

Briefly, describe evidence for convergence of circuits within the basal ganglia.

A

Massive number of cerebral cortical cells -> smaller numbers (75 mil) of striatal neurons -> even smaller numbers (0.7 mil) of globus pallidus neurons

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13
Q

(OBJ) Describe the MOTOR LOOP in terms of functional organization: cortical input, striatum, pallidum, thalamus, and output.

A

MOTOR LOOP: controls body movement

  • -Input: motor, premotor, somatosensory cortex
  • -Striatum: putamen
  • -Pallidum: internal segment of GP
  • -Thalamus: VL/VA nuclei
  • -Output: primary motor, premotor, supplementary motor cortex
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14
Q

(OBJ) Describe the OCULOMOTOR LOOP in terms of functional organization: cortical input, striatum, pallidum, thalamus, and output.

A

OCULOMOTOR LOOP: controls eye movement

  • -Input: posterior partietal, prefrontal cortex
  • -Striatum: caudate
  • -Pallidum: internal segment of GP; substantia nigra pars reticulata (-> superior colliculus)
  • -Thalamus: mediodorsal, VA nuclei
  • -Output: frontal eye field, supplementary eye field
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15
Q

(OBJ) Describe the PREFRONTAL CORTICAL LOOP in terms of functional organization: cortical input, striatum, pallidum, thalamus, and output.

A

PREFRONTAL CORTICAL LOOP: involved in executive functions of the brain

  • -Input: dorsolateral prefrontal cortex
  • -Striatum: anterior caudate
  • -Pallidum: internal segment of GP; substantia nigra pars reticulata
  • -Thalamus: mediodorsal, VA nuclei
  • -Output: dorsolateral prefrontal cortex
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16
Q

(OBJ) Describe the LIMBIC LOOP in terms of functional organization: cortical input, other input, striatum, pallidum, thalamus, and output. (This loop should be described in greater detail than the others.)

A

LIMBIC LOOP:

  • -aka ventral striatal system or orbital medial prefrontal cortical loop
  • -Involved in emotional responsiveness and control of mood and behaviors
  • -More ventrally placed
  • -Input: amygdala, hippocampus, orbitofrontal cortex, anterior cingulate cortex, temporal cortex
  • —Also get inhibitory dopaminergic (D3/D4) input from ventral tegmental area of midbrain [mesolimbic dopamine reward system]
  • -Striatum: ventral striatum (nucleus accumbens)
  • -Pallidum: ventral pallidum of GP
  • -Thalamus: mediodorsal nucleus
  • -Output: anterior cingulate, orbital frontal cortex
17
Q

(OBJ) Explain the principle of center-surround inhibition in the basal gangliar circuits. Give an example of how this works.

A

Indirect pathway -> background of inhibition (surround)
–Suppresses extraneous movements

Direct pathway -> highly focused excitatory feedback loop (center)
–Facilitates selected movements

Ex. eye movement

  • -Substantia nigra pars reticulata (SNPR) normally inhibits superior colliculus
  • -Activation of caudate nucleus inhibits tonic activity of SNPR, disinhibiting superior colliculus and allowing eye movement to take place
  • —-> Keeps eyes from jerking around all the time/moving when you don’t want them to
18
Q

True/false: the model of direct and indirect pathways in the basal ganglia is highly simplified.
–Explain your answer.

A

TRUE; there are large numbers of other regulatory interneurons in the striatum, forming a patchwork of NTs

19
Q

Briefly, what is a striasome?

A

An isolated island of specific neurotransmitter within the basal ganglia (this is not very important)

20
Q

True/false: in all but the simplest movements, there is activity in neurons of the basal ganglia and cerebellum before the movement begins and before there is activity in the primary motor cortex.
–Explain your answer.

A

TRUE; this activity is required in order to assure proper motor patterns are selected, while inhibiting extraneous or detrimental ones.

21
Q

What components are involved in the mesolimbic dopamine reward system? (5)

A

D3/D4 dopaminergic projections from VENTRAL TEGMENTAL AREA to NUCLEUS ACCUMBENS (striatum) in limbic loop -> VENTRAL PALLIDUM -> MD of THALAMUS -> LIMBIC CORTEX

22
Q

If a patient has a loss of neurons in the substantia nigra pars compacta (as in Parkinson’s), what nuclei wind up being overactive? (2)

A

SUBTHALAMIC NUCLEUS - loss of D2 dopaminergic neurons that normally INHIBIT the inhibitory neurons to the globus pallidus externa -> inhibition of globus pallidus externa’s tonic inhibition of the subthalamic nucleus -> disinhibition of the subthalamic nucleus -> overactive subthalamic nucleus

GLOBUS PALLIDUS INTERNA - loss of D1 dopamine neurons that normally activate the inhibition of this area result in it being overactive
–Also becomes even more activated by the overactivated subthalamic nucleus

23
Q

What other nucleus of the extrapyramidal system is most similar functionally to the substantia nigra pars reticulata?

A

Globus pallidus interna - both function as the “pallidum” in certain loops
–SNPR is involved in the oculomotor loop – gets inhibited by the caudate, releasing its tonic inhibition on the mediodorsal/VA nuclei of the thalamus and allowing eye movement to happen

24
Q

What is the difference between the pars compacta and pars reticulata?

A

Pars compacta: dopamine neurons that project to caudate and putamen

Pars reticulata: no dopamine neurons; instead, neurons are functionally/structurally like the neurons of the globus pallidus interna (tonic GABAergic inhibitory neurons

25
Q

In the planning and execution of a skilled motor pattern, what is the most likely sequence of activation of cerebral cortical regions?

A

Parietal lobe -> supplementary motor/premotor cortex -> primary motor cortex

  • -Complex movements that require planning begin with activity in the parietal cortex posterior to the postcentral gyrus
  • -Suggests substantial need for integration of sensory functions prior to initiation of movement
26
Q

(OBJ) Describe the physiology of current medications for Parkinson. (2)

A

Levodopa: directly replace dopamine; only active once it gets into brain

Amantadine: a weak NMDA glutamate antagonist

27
Q

List some clinical features of Parkinson’s disease. (3 diagnostic symptoms, onset, other symptoms)

A

Resting tremor
Rigidity
**Bradykinesia
Insidious onset, unilateral to bilateral

Other: masked face, hypovolemic speech, swallowing difficulty, micrographia, stooped posture, shuffling gait, start hesitancy and freezing; difficulty arising from a chair and turning over in bed, hypophonic speech, sialorrhea, loss of sense of smell, foot dystonia

27
Q

What causes Huntington’s disease?

A

Chromosome 4p - IT15 gene has trinucleotide repeat sequences that, when expanded, cause disease

Balance between direct and indirect pathway so that indirect pathway degenerates first -> unencumbered direct pathway activity -> involuntary movements
Loss of caudate and putamen

28
Q

List three types of hyperkinesias and the lesions that cause them: athetosis, hemiballism, dystonia (focal and generalized)

A

Athetosis: slow writing, snakelike movements caused primarily by lesions of the striatum

Hemiballism: the appearance of flailing, ballistic, undesired movements of the limbs, due to acute lesions of the subthalamic nucleus

Dystonia: twisting of the limbs, trunk, or neck due to structural or functional abnormality of the basal ganglia

  • -Learned motor patterns expand -> agonist/antagonist muscles no longer coordinated, can act at the same time -> painful twisting of limbs, trunk, or neck
  • -Focal dystonia often happens in professional musicians (embouchure, fingers, etc)
  • -Can also occur as generalized dystonia - more congenital
29
Q

(mOBJ) Knowing the circuit changes in Parkinson’s disease, what targets would be favorable for surgical ablation? What alternatives to ablation are now available?

A

Globus pallidus interna: reduces akinesia by reducing overactive tonic inhibition

Deep brain stimulation of globus pallidus or subthalamic nucleus now possible - electrode stimulation of targeted brain region

Gene therapy also emerging as a possible treatment