#19 - Basal Ganglia Flashcards
1
Q
Components
A
- Caudate nucleus
- Putamen
- Globus pallidus
- Nucleus accumbens
- Olfactory tubercle
2
Q
Dorsal Striatum Components
A
- Caudate Nucleus
- Putamen
3
Q
Lentiform Nucleus Components
A
- Putamen
- Globus pallidus
4
Q
Ventral Striatum Components
A
- Nucleus accumbens
- Olfactory tubercle
- Also includes ventral parts of caudate and putamen (basal forebrain)
5
Q
Sub-components of Basal Ganglia Network
A
- Substantia nigra
- Delivers dopamine to the striatum (caudate nucleus + putamen)
- Subthalamic nucleus
- Below the thalamus
- Inhibitor of movement
6
Q
Medium Spiny Neurons
A
- Constitute 95% of neurons in striatum
- Synthesize, release GABA; inhibit targets
- Store complex activity patterns
- Two types
- With D1 dopamine receptors
- Project to internal segment of globus pallidus
- Excited by dopamine
- With D2 dopamine receptors
- Project to external segment of globus pallidus
- Inhibited by dopamine
- With D1 dopamine receptors
7
Q
Substantia Nigra Components
A
- Pars Compacta
- Black
- Contains dopamine-synthesizing neurons
- Provides DA to MSNs in striatum
- Degernation = Parkinson’s
- Pars Reticulata
- NOT black
- Continuation of internal globus pallidus
- Releases GABA, constantly active (like GPi)
8
Q
Direct BG Pathway
A
- Direct pathway: “go”
- Facilitates expression of a desired motor behavior
- Activated by cortex
- Direct = fewer steps to affect GPi/SNr
- Cortex activates direct pathway, excites D1 MSNs
- Excited D1 MSNs project to, inhibit GPi that are constitutively firing (GPi constitutively inhibit thalamus)
- Inhibited GPi frees VA thalamus from inhibition
- VA thalamus excites SMA/PMA to excite M1 neurons
9
Q
Indirect BG Pathway
A
- Indirect pathway: “no go”
- Suppresses expression of undesired motor behaviors, terminates movement
- Activated by cortex
- Indirect = more steps to affect GPi/SNr, involving GPe control of STN
- Remember, GPe is constitutively firing (inhibiting STN)
- But when…cortex (PMA/SMA) excites D2 MSNs
- Excited D2 MSNs project to, inhibit the inhibitory GPe
- Disinhibited GPe frees STN from inhibition (GPe constitutively inhibits STN)
- Uninhibited STN excites the GPi
- Excited GPi inhibits the VA thalamus more than usual
- So VA thalamus does not excite the SMA/PMA
10
Q
Dopamine on BG Pathways
A
- Dopamine is excitatory to MSNs containing D1 receptors
- D1 containing MSNs form the direct pathway to GPi and SNr
- Excitation of these direct MSNs -> inhibition of GPi, SNr -> reduced inhibition of thalamus -> movement
- Dopamine is inhibitory to MSNs containing D2 receptors
- D2 containing MSNs form the indirect pathway to GPi and SNr
- Inhibition of these indirect MSNs -> reduced inhibition of GPe neurons -> reduced excitation by STN to GPi, SNr -> also reduced inhibition of thalamus -> movement
11
Q
Basal Ganglia Disorders
A
- Hypokinetic: Parkinson’s
- Hyperkinetic: Huntington’s Chorea
- Hemiballismus: lesion in subthalamic nucleus
- Hyperkinetic disorder like the choreas, but affecting more proximal limb movements
- Very intense movements
- Progressive supranuclear palsy: neuronal degeneration in the STN, SNr, and globus pallidus
- Tourette syndrome
- Several dystonias
12
Q
Parkinson’s Disease
A
- Hypokinetic disorders = akinesia (absence or paucity) and bradykinesia slowness of movement)
- Parkinson’s: progressive loss of dopaminergic neurons in the SNc
- Results in a substantial decrease in dopamine in the striatum (primarily the putamen)
- Leads to:
- Loss of excitation of direct pathway MSNs -> increased inhibition (loss of disinhibition) of VA thalamus by GPi, SNr
- Loss of inhibition of indirect pathway MSNs -> increased activity in STN, increased inhibition of the thalamus by GPi, SNr
- Increased thalamic inhibition reduces motor cortex activity leading to akinesia
- Basically, direct pathway has trouble winning
- Three cardinal signs to Parkinson’s disease (diagnosis requires 2 of 3)
- Bradykinesia: slowness of movement
- Difficulty starting and planning movements, and each movement has to be carefully planned
- Resting Tremor
- Probably because we have a lot of BG circuits for hand movement
- Rigidity: a kind of hypertoniaRemember: rigidity is extrapyramidal in nature
- Same resistance in all directions
- Not velocity dependent
- Contrast with spasticity
- When BG are involved in “cogwheel” phenomenon, can often be elicited
- Bradykinesia: slowness of movement
- Treatment for Parkinson’s is aimed at reducing inhibition of the thalamus
- Use of DA precursor L-DOPA to restore striatal dopamine levels
- Lesion of the GPi (pallidotomy) to reduce thalamic inhibition
- High frequency stimulation of the subthalamic nucleus to “jam” its excitatory input to GPi/SNr
13
Q
Huntington’s Disease
A
- Chorea = sudden, involuntary and purposeless jerking movements of the head, limbs, and trunk
- Pathology: degeneration of MSNs in the striatum (mostly the caudate)
- Leads to loss of inhibition in the thalamus and increased activity in motor cortex
- Hyperkinetic Disorder
- Basically, brain had harder time preventing/terminating movement, so pt has too much movement
- Note:
- D2 MSNs are the first to be lost in Huntington’s chorea
- This loss of MSNs in the indirect pathway increased inhibition of the STN by GPe
- Don’t prevent movement as well as they should, so lots of extra movement
- Loss of excitatory input (from STN) to GPi/SNr reduces inhibition of thalamus
- This is not a dopamine problem
14
Q
Basal Ganglia Blood Supply
A
- Head of Caudate Nucleus
- ACA via recurrent artery of Heubner (aka medial striate artery)
- Body of Caudate Nucleus
- MCA via lenticulostriate arteries & other deep branches
- Tail of Caudate Nucleus, GPi, Internal capsule
- Anterior choroidal artery
- Putamen and globus pallidus
- MCA via lenticulostriate arteries (internal pallidal segment is also supplied by the anterior choroidal artery)
15
Q
Basal Ganglia Functions
A
- BG gets certain M1 corticospinal neurons firing, but not others, to achieve desired behavioral outcomes that are learned and reinforced
- In the resting state, the BG system suppresses movement by inhibiting the VA thalamus, thereby suppressing PMA, SMA activity
- Initiates movements
- Suppress non-synergistic movements
- “Chunk” elements into action sequences
- Encode procedural memories (how you learn to do new things with your body) so that behaviors can be automated
- Control (via pedunculopontine nucleus (PPN) in midbrain) activation of locomotor pattern generators
