Basal Ganglia

Question 1

describe the components of the basal ganglia

Answer 1

• striatum: caudate, putamen, ventral striatum
• globul pallidus: external (lateral) part (GPe), internal (medial) part (GPi)
  
  • the GPi is the chief output nucleus
• subthalamic nucleus
• substantia nigra: pars reticulata and pars compacta

Question 2

Answer 2

Question 3

Answer 3

Question 4

explain how basal gangliar influences motor activity

Answer 4

• the thalamus and, indirectly, the frontal cortex, are under tonic inhibitory control from GPi
  
  • this inhibition is modulated by two parallel basal gangliar pathways that originate in and diverge from the striatum
• one direct and one indirect pathway
  
  • the activation of the direct pathway disinhibits the thalamus resulting in the facilitation of movement
  • the indirect pathway inhibits the thalamus which diminishes movement

Question 5

describe the direct basal gangliar pathway

Answer 5

• striatal GABAergic output supresses activity in the GPi
• decreased GABAergic output from the GPi increases thalamic activity (disinhibition)
• increased thalamic glutamate activity increases cortical activity to facilitate movement

Question 6

draw out the direct basal gangliar pathway

Answer 6

Question 7

describe the indirect basal gangliar pathway

Answer 7

• striatal GABAergic output suppresses activity in the GPe
• decreased GABAergic output from the GPe increases excitatory glutamatergic output from the subthalamus, activating GPi
• GPi activity is increased, leading to thalamic inhibition via GABA
• decreased thalamic output decreases cortical activity, thereby diminishing movement

Question 8

draw out the indirect basal gangliar pathway

Answer 8

Question 9

describe the function of dopamine on the direct pathway

Answer 9

• DA released from the SNc (sub. niga pars compacta) excites striatal cells of the direct pathway (i.e. those expressing D1R)
• striatal ouput suppresses activity in the GPi
• decreased output from the GPi disinhibits thalamus
• increased thalamic activity increases cortical activity to facilitate movement

Question 10

draw out the action of dopamine on the direct pathway

Answer 10

Question 11

describe the action of dopamine on the indirect pathway

Answer 11

• dopamine inhibits striatal cells of the indirect pathway (i.e. those expressing D2R)
• decreased striatal output allows disinhibition of the GPe
• increased output from the GPe inhibits the Sth
• decreased ouput from the subthalamus (Sth) decreases activity within the GPi
• decreased activity within the GPi disinhibits the thalamus
• increased thalamic ouput increases cortical activity, thereby facilitating movement

Question 12

draw out the action of dopamine on the indirect pathway

Answer 12

Question 13

describe neurobiology in Parkinson disease

Answer 13

• insufficient release of dopamine alters activity in both direct and indirect pathways, decreasing inhibition of the globus pallidus internal (GPi)
  
  • increased thalalmic inhibition
  • decreased cortical activity and hypokinesis

Question 14

____ cells are among the degenerating cells

Answer 14

catecholaminergic cells are among the degenerating cells

• nigral dopaminergic cells
• noradrenergic pontine locus coeruleus
• autonomic noradrenergic cells

Question 15

describe clinical features of Parkinson disease

Answer 15

• tremor (fasting)
• rigidity
• bradykinesia
• decreased facial expression
• short strides
• flexion of trunk
• akinesia
• abnormal postural adjustments

Question 16

describe the front-line therapy for Parkinson disease

Answer 16

• oral L-dopa increases dopamine synthesis in surviving neurons of the SNc
• carbidopa reduces peripheral metabolism of L-dopa
• treatment with L-dopa/carbidopa becomes less effective over several years

Question 17

describe the function of dopamine receptor agonists

Answer 17

• drugs that activate either or both D1 and D2 receptors can normalize movement, bypassing degenerating nigrostriatal neurons and acting directly on postsynaptic receptors

Question 18

describe antiviral therapy in treating Parkinson disease

Answer 18

• antiviral therapy may benefit some manifestations of Parkinson disease (akinesia, rigidity)
  
  • may promote the release of dopamine and/or block ACh receptors (also weakly blocks NMDA receptors)

Question 19

describe dopamine metabolism inhibitors in treating Parkinson disease

Answer 19

• inhibitors of MAO
  
  • blockage of monoamine oxidase-B (MAO-B)
    
    • may improve responses to or delay the need for other therapies
• inhibitors of COMT
  
  • may be given in addition to L-dopa and carbidopa

Question 20

describe the function of anticholinergics in treating Parkinson disease

Answer 20

• acetylcholine excites striatal neurons that express D2 receptors
• ACh (acting on muscarinic receptors) and dopamine (acting on D2 receptors) exert opposite effects on striato-pallidal cells
• muscarinic antagonists (binding to muscarinic receptors) therefore suppress acetylcholine-mediated excitation of striatal neurons in the indirect pathway

Question 21

describe surgical ablation sites in treating Parkinson disease

Answer 21

• subthalamus
• globus pallidus internal

Question 22

describe other causes of Parkinsonian conditions

Answer 22

• drug induced
  
  • antipsychotic drugs (DA receptor blockers)
  • depletors of DA stores (reserpine)
  • toxic contaminants (MPTP)
• vascular
  
  • strokes disrupting nigrostriatal pathway
• traumatic
  
  • multiple blows to the head can damage the midbrain
• postencephalictic
  
  • viral encephalitis can lead to nigral degeneration
• neoplastic
  
  • tumors can disturb the nigrostriatal system

Question 23

describe neurobiology in Huntington disease

Answer 23

• destruction of striatal neurons that express D2 receptors
• reduced inhibition of thalamus via indirect pathway leads to increased cortical activity, leading to hyperkinesis

Question 24

describe the treatment for Huntington disease

Answer 24

• antidepressants can be useful in combating associated depressions
• D2 receptor antagonists can exert some antichoreatic effect (assuming some surviving striatal neurons expressing this receptor)
• vesicular monoamine transporter (VMAT) inhibitors

Question 25

describe hemiballismus

Answer 25

• hemiballismus commonly reflects unilateral stroke-related injury to the subthalamus with contralateral limbs being affected
• following such injury, excitatory output to GPi decreases
• the thalamus is disinhibited, yielding increased cortical excitation
• contralateral ballismus can result (often expressed as flinging and rotational movements of the arm and leg)