Motor Systems 4 Basal Ganglia - Ebner Flashcards
A female in her early thirties has begun developing uncontrolled voluntary movements. It seems to be getting worse. She is adopted so you do’t have ny a family history.
Her partner is especially worried about her loss of mental function.
What might be the diagnosis?
Maybe could be mutliple things, but sounds a lot like Huntington’s
What are the 4 parts of the basal ganglia?
Neostriatum
Globus Pallidus
Substantia Nigra
Subthalamic Nucleus
Neostriatum consists of what two structures?
Caudate and putamen
What are the primary output neurons of the neostriatum?
they also receive inputs FYI
Spiny neurons
What neurotransmitters do spiny neurons use?
Mostly GABA
1 group is GABA and Substance P
1 group is GABA and Enkephalin
Describe the afferent projection to the striatum:
Corticostriate projection - Cortex to striatum
Originates in many areas - ex Premotor and Motor
Excitatory and Glutamate
Describe the striatum’s direct pathway:
Striatum GABA/SP project to inhibit GPi
GPi projects to inhibit VL and VA of thalamus
Striatum GABA/SP also project to inhibit SNr
SNr also inhibits VA/VL of thalamus and brainstem
Thalamus (VA/VL) activates cortex
Brainstem (superior colliculus for eye movements and pedunculopontine nuclei for locomotion)
What is the indirect pathway of the striatum?
Striatum GABA/ENK cells inhibit the GPe
GPe inhibits STh (with GABA)
STh excites GPi and SNr (with glutamate)
(Like before, GPi and SNr go on to inhibit the thalamus)
What is the hyperdirect pathway?
Pathway that uses glutamate, the cortex directly activates the STh (subthalamic nucleus)
Briefly mentioned in class….
Describe the Substantia Nigra Pars Compacta pathway? (SNc)
So the SNc uses dopamine to both stimulate and inhibit depending on the target’s receptors
It activates the GABA/SP neurons of the Striatum through D1 receptos.
It inhibits the GABA/ENK neurons of the Striatum via D2 receptors
GABA/SP neurons go on to inhibit the SNc and GPi/SNr
GABA/ENK neurons go on to inhibit the GPe in the indirect pathway
So what part of the basal ganglia is sort of tonically keeping motor movement from happening?
What has to happen to make motor movement occur?
GPi is inhibiting the thalamus and motor activity
GPi must be inhibited for motor to happen
Use eye movement to show what happens in the basal ganglia to make movement happen:
Caudate receives excitatory signal from frontal eye fields
Direct and indirect pathways decrease SNr activity
Thalamus is activated and disinhibits superior colliculus
Saccades produced!
How would a crazy increase of Dopamine affect the basal ganglia?
DA will decrease GABA/ENK activity, so GPe stays active. GPe inhibits STh so that it cannot excite GPi/SNr at all
GABA/SP cells are activated and directly inhibit GPi and SNr a lot.
GPi/SNr is now out of the picture, causing the thalamus to stimulate cortex motor activity A LOT!
Lots of involuntary motor movements.
What’s a great way to get full of dopamine activity?
Cocaine or meth
I mean, that’s not great, but that’s what happens
What will result from a Subthalamic nucleus lesion?
Why?
Ballismus!
Wild exaggerated limb movements
Getting rid of STH is going to decrease major stimulus to GPi/SNr
Thalamus and cortex hyperactive
What kind of problem creates Parkinson’s disease?
Main pathology behind disease is loss of pigmented cells in substantia nigra pars compacta (SNc).
SNc can’t inhibit GABA/ENK, so they inhibit GPe, which sets STh free to activate GPi/SNr
SNc can’t excite GABA/SP cells to inhibit GPi/Snr
SO. Thalamus stays inactivated so movements are very slow
4 main clinical findings of Parkinson’s?
Bradykinesia (slow movement and reflex)
Rigidity
Resting tremor
Postural Instability
Treatment for Parkinson’s?
Restore dopamine using L-dopa
dopamine can’t pass BBB
What happens if you get a lesion in your globus pallidus?
Symptoms?
Why?
Dystonia: sustained twisting and repetitive muscle contractions
Caused by an increase in motor activity because the GPi can no longer inhibit thalamus activity
What will striatal lesions in the two different regions cause?
- Putamen
- Associated with motor cortical areas
- Get stereotypic motor hyperactivity - Caudate
- related to prefrontal cortex/premotor /SMA
- Changes in more “complex behavior”
* Vulgarity
* Increased appetite/polydipsia
* Hypersexuality
What is the pathology of Huntington’s Disease?
Including genetics.
Genetic:
- Abnormal short arm of Chromosome 4
- CGA repeat creates gain of function
- Onset 25-40 yrs old
Path:
- Death of spiny neurons in Striatum
- Especially GABA/ENK
- Death of full Striatum and cortex follows
Symptoms of Huntington’s Disease?
Involuntary movements as indirect pathway affected
Chorea - brief, repetitive, jerky, uncontrolled movements
Athetosis - slow, involuntary, convoluted, writhing
Dementia and personality changes
Akinesia as direct pathway is affected
- loss of voluntary movement
Describe the striatum’s direct pathway:
Striatum GABA/SP project to inhibit GPi
GPi projects to inhibit VL and VA of thalamus
Striatum GABA/SP also project to inhibit SNr
SNr also inhibits VA/VL of thalamus and brainstem
Thalamus (VA/VL) activates cortex
Brainstem (superior colliculus for eye movements and pedunculopontine nuclei for locomotion)
What is the indirect pathway of the striatum?
Striatum GABA/ENK cells inhibit the GPe
GPe inhibits STh (with GABA)
STh excites GPi and SNr (with glutamate)
(Like before, GPi and SNr go on to inhibit the thalamus)
