12 - Basal Ganglia Flashcards
What are two extrapyramidal diseases?
Huntington’s Disease
Parkinson’s Disease
Why did Huntington’s and Parkinson’s disease provide early information on the basal ganglia?
Both characterised by motor dysfunction and BG degeneration
So, the idea that the BG is involved in execution of movement, but anatomically BG has NO direct projections to any motor output structures
In terms of what the BG does, what did electrophysiology demonstrate?
Neurons in BG very active before and during movement, but ALWAYS AFTER cortex is active
Neural activity in BG does NOT code for particular movements (responsible for coding of activity)
What does the anatomy of the BG show about it’s connectivity?
Bg forms closed feedback loops with cortex and thalamus
Via Striatum -> globus palidus -> thalamus
Describe the direct path of feedback in the BG from the cortex to thalamus.
Via Globus Pallidus pars interna (GPi)
Positive Feedback Loop
Cortex to striatum: excitatory (glutamagenic)
Striatum to GPi: inhibitory (GABA)
GPi to thalamus: inhibitory
Thalamus to cortex: excitatory
Increases excitatory thalamocortical feedback
Increased inhibition of GPi decreases inhibition of thalamus, so it increases activity onto cortex.
Describe the two indirect paths in the BG from cortex to thalamus
Both Negative Feedback
Via GP pars externa (GPe)
- Cortex - e > striatum
- Striatum - i > GPe
- GPe - i > GPi (weaker)
- GPi - i > thalamus (stronger due to previous reduction)
- thalamus - e > cortex (weaker)
Via Subthalamic nucleus (STN)
- Cortex - e > striatum - i > GPe (stronger) - i > STN (weaker) - e > GPi (stronger) - i > thalamus (stronger) - e > cortex (weaker)
Briefly describe the models of basal ganglia function
“Scaling of movement”
- direct loops helps to initiate movement
- indirect loops help to stop movement
“Focusing”/”Filtering” of movement
- direct loops BOOSTS appropriate motor programmes (from CPG)
- indirect loop FILTERS OUT inappropriate motor programs (from competing CPG; exaggering difference in similar movements so there’s a ‘winner’)
Error Connection
- BG loops provide central feedback to cortical response systems
- Provide predictive feebdack
What provides the diversity of BG function?
Multiple parallel loops
Diverse projections to striatum, all from different cortical regions and they remain segregated
What does dopamine input do to the BG loops?
Substania Nigra projects dopamine to D1 and D2 receptors at striatum.
D1 project to GPi, and D2 to GPe.
DA acts at D1 to increase inhibition from striatum -> GPi, increases activity on direct pathway -> increases cortical activity
DA acts at D2 to decrease inhibition from striatum to GPe (indirect loops). Reduced activity on indirect pathway, so positive feedback stronger.
Why do amphetamines (DA agonists) increase excitatory information in the cortex?
Drugs enhance positive feedback and reduce negative feedback in cortex.
What are the main symptoms of Huntington’s Disease and what type of neurons are predominately affected?
Progressive loss of GABA neurons in striatum (especially in caudate nucleus)
Twitches in face and hands, progresses to tremors through body.
Can resemble voluntary movements.
Associated with dementia.
How can Huntington’s Disease symptoms be explained in terms of the BG loop?
Loss of GABA neurons in striatum lead to decreased output from GPi to thalamus
STN is not exciting GPi, so GPi loses activity to thalamus, so thalamus increases activity to cortex.
Boosts positive feedback to cortex.
Inappropriate motor programmes are not FILTERED OUT, and so intrude into behaviour
What are the main symptoms of Parkinson’s disease and what type of neurons are predominately affected?
Progressive disease, great difficulty in moving and initiating acting (“sticking”), abnormal gait and don’t swing arms. also, resting tremor.
Degeneration of DA-containing neurons in substantia nigra, that project to caudate and putamen
What is the difference between a resting and essential tremor?
Resting: present when limb is at rest
Essential: common in elderly, tremor when attempting to do something.
How can Parkinson’s Disease symptoms be explained in terms of the BG loop?
Death of neurons in SN leads to loss of dopamine input to BG.
Loss of DA input leads to filter being closed, blocking all motor signals (appropriate and inappropriate) from cortex. So, initiating of movement difficult.
Get a lot of GPi excitation, so thalamus is strongly inhibited, little feedback from thalamus to cortex.
Cortex isn’t getting enough excitatory input to produce movement.
