The Basal Ganglia Flashcards
What structures are part of the basal ganglia?
What structure is an important part of this same system?
Caudate Putamen Globus Pallidus
Substantia Nigra
What are the two “extrapyramidal” diseases that gave us a good understanding of the basal ganglia?
Huntington’s Disease Parkinson’s Disease
–> these diseases quite selective for BG and are disorders of movement
Connections of the BG go to the ______. They have no ______ projections to any motor output structures (BS, red nucleus, motor cortex). From electrophysiology we know that neurons in the BG are very active _____ and _____ movement, but always _____ activation of the cortex. Unlike some areas such as the motor cortex, there does not appear to be neurons for a ______ purpose (so you cannot record activity and predict movement)
thalamus
direct
before
during
after
The BG forms a closed loop with the cortex - the motor cortex mainly but laso other cortical areas
What does the striatum refer to?
Striatum = Caudate + Putamen
There are 3 distinct closed loops involving the BG.
- The Direct Path via _____ ______ and pars _______ (GPi) - excitatory
- The Indirect Path via _____ ____ and pars _______ (GPe) - inhibitory
- The Indirect Path via _______ _______ (STN) - inhibitory
Globus Pallidus
interna
Globus Pallidus
externa
subthalamic nucleus
Draw the Direct Path
Draw the Indirect Path with the pars externa
Draw the Indirect Path with the subthalmic nucleus
MODELS OF BG FUNCTION - not mutually exclusive
What do they think are the function of these loops in MODULATING programs originating in the cortex?
They allow the cortex to modulate it’s own activity - “scale” the movements.
Detect how much excitatory feedback it gets and can then increase inhibitory feedback
and/or excitiatory feedback initates/increases movements, and inhibitory feedback stops/decreases movements.
BUT there’s more to the story
MODELS OF BG FUNCTION - not mutually exclusive
It is also thought that the BG is involved in the ______ (or selecting) of movement - _______/______ of movement. There are lots of clusters of neurons and different motor ______ vying for control. The motor cortex needs to select the movement to _______. So some activity is _______ (fed through direct loop) and some is ______ (fed through indirect loop)
______ processes may influence this filtering as 10% of striatal neurons respond to _______ (mechanism by which learning can allow reward), These neurons DO NOT have projections outside the striatum.
–> like a stereo amplifier. Needs to filter out the noise.
filtering
focusing/filtering
programs
execute
boosted
suppressed
Reward
reward
MODELS OF BG FUNCTION - not mutually exclusive
The BG could also be involved in ______ correction. they provide internal _______ to the cortex that allows it to predict the movement, then ______ it if necessary. So it uses feedback to _____ the movement. This internal circuit recognises errors from _______ and adjusts _________.
Eg: reaching out - detecting error and adjusting. You can do it externally, with eyes - but it’s slow. External information has to be fed back through….by the time you’ve detected it you’re going to be way off course.
error
feedback
correct
scale
learning
on-the-fly
There are multiple parallel loops orignating from different cortical regions…these remain segregated throughout the BG and return to the cortical areas of origin. This suggests….
The BG has a strong diversity of function. We understand it’s role in movement the best, but it’s probably also involved in thought/cognition. So filtering thoughts, planning, selecting, anticipating, correcting, etc
The dopamine input to the BG comes from the ______ ______ and projects to the _________. Overall, dopamine ______ the activtiy of BOTH the direct and indirect loops. It ______ activity of the direct loop and ______ activity of indirect loop.
There are two types of dopamine ________, D1 and D2. The D1 receptors are ______ and involved in the ______ loop. Hence, the D1 receptors _______ the inhibiton of the GPi, which _______ inhibition of the thalamus and ______ cortical activity.
The D2 receptors are _______ and involved in the _______ loop. They decrease the ______ connections between the _______ and the GPe. This means there is _____ inhibition of the GPi and _____ inhibition of the thalamus, boosting cortical activity. Similarly, there is more inhibiton of the cpnnections from the GPe to the ______ _____ nucleus. This further ______ the GPi, and again decreases it’s _______ of the thalamus.
substantia nigra
striatum (putamen and caudate)
increases
boosts
suppresses
receptors
excitatory
direct
increase
decreases
boosts
inhibitory
indirect
inhibitory
striatum
more
less
subthalamic nucleus
inhibits
inhibition
Thinking of DA in the context of the filter…it’s allowing _____ stuff through the direct loop and _____ stuff through the indirect loop. So overall this is a _____ effect which results in overall ______ in movement.
more
less
stimulant
increase
Huntington’s Disease is a movement disorder accompanied by dementia. There is a gradual loss of _____ neurons in the ______ (especially the caudate nucleas). It’s symptoms are _____ movements intruding into their behaviour. They have _____ in the face, hands and progress to _____ in the body (face/hands strongly represented in the cortex).
The net effect is a _______ in activity of the globus pallidus, which leads to ______ inhibition of the thalamus and an increase in cortical activity (while there is some decrease of the direct loop, overall the decrease in indirect loops leads to this net effect)
GABA
striatum
uncontrolled
twitches
tremours
decrease
less
Parkinson’s Disease leads to great difficulty ______, particularly ______ actions. There is an abnormal ____ (shuffling) and patients have issues ______ their arms. There is also a ______ tremour (NOT one that occurs when conducting a movement which is common in older people).
The pathology is a ________ of DA neurons in the ________ _____ that project to the caudate and putamen. We know that overall DA ______ activity in the BG which explains the symptoms. The overall effect is for the GPi to be ______ active, which _______ inhibition of the thalamus and _______ cortical excitation.
moving
initiating
gait
swinging
degeneration
substantia nigra
boosts
more
increases
decreases
Describe the 4 treatment options for Parkinson’s Disease
- DA agnosit drug - precursor to DA to increase DA availability - called L-dope. BUT there is a degeneration of the neurons themselves so there is a decrease in this drugs effectiveness as the disease progresses.
- Cell transplants - implants healthy new cells into substantia nigra - BUT it didn’t work - killed off the new cells too. Whatever was causing the disease was still there. However, it did work for people poisoned with MPTP (neurotoxin). Didn’t recoiver lost neurons but stopped disease progression.
- Brain lesions to GPi or STN (sometimes used)
- Deep brain stimulation of STN. This decreases it’s activity to STOP excitation of the GPi, so pars interna not as active as it normally is. Doesn’t kill neurons as leison does, and level of stimulation ca be adjusted.
