Basal Ganglia Flashcards
1
Q
describe the components of the basal ganglia
A
- 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
2
Q
A
3
Q
A
4
Q
explain how basal gangliar influences motor activity
A
- 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
5
Q
describe the direct basal gangliar pathway
A
- 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
6
Q
draw out the direct basal gangliar pathway
A
7
Q
describe the indirect basal gangliar pathway
A
- 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
8
Q
draw out the indirect basal gangliar pathway
A
9
Q
describe the function of dopamine on the direct pathway
A
- 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
10
Q
draw out the action of dopamine on the direct pathway
A
11
Q
describe the action of dopamine on the indirect pathway
A
- 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
12
Q
draw out the action of dopamine on the indirect pathway
A
13
Q
describe neurobiology in Parkinson disease
A
- 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
14
Q
____ cells are among the degenerating cells
A
catecholaminergic cells are among the degenerating cells
- nigral dopaminergic cells
- noradrenergic pontine locus coeruleus
- autonomic noradrenergic cells
15
Q
describe clinical features of Parkinson disease
A
- tremor (fasting)
- rigidity
- bradykinesia
- decreased facial expression
- short strides
- flexion of trunk
- akinesia
- abnormal postural adjustments
16
Q
describe the front-line therapy for Parkinson disease
A
- 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
17
Q
describe the function of dopamine receptor agonists
A
- drugs that activate either or both D1 and D2 receptors can normalize movement, bypassing degenerating nigrostriatal neurons and acting directly on postsynaptic receptors
18
Q
describe antiviral therapy in treating Parkinson disease
A
- 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)
19
Q
describe dopamine metabolism inhibitors in treating Parkinson disease
A
- inhibitors of MAO
- blockage of monoamine oxidase-B (MAO-B)
- may improve responses to or delay the need for other therapies
- blockage of monoamine oxidase-B (MAO-B)
- inhibitors of COMT
- may be given in addition to L-dopa and carbidopa
20
Q
describe the function of anticholinergics in treating Parkinson disease
A
- 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
21
Q
describe surgical ablation sites in treating Parkinson disease
A
- subthalamus
- globus pallidus internal
22
Q
describe other causes of Parkinsonian conditions
A
- 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
23
Q
describe neurobiology in Huntington disease
A
- destruction of striatal neurons that express D2 receptors
- reduced inhibition of thalamus via indirect pathway leads to increased cortical activity, leading to hyperkinesis
24
Q
describe the treatment for Huntington disease
A
- 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
25
Q
describe hemiballismus
A
- 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)
