Basal Ganglia Motor System Flashcards
What are the 4 major components of the basal ganglia?
neostriatum
globus pallidus
substantia nigra
subthalamic nuclei
What area of the basal primarily receives the inputs and what part sends the outputs?
neostriatum gets the inputs
globus pallidus sends the outputs
(substantia nigra and subthalamic nucleus are internal circuitry)
The neostriatum consists of what two structures?
caudate and putamen
What are the two type of neurons in the neostriatum?
- spiny neurons - get the input and send the output
- aspiny neurons - the interneurons
THrough what pathway does info from the cortex reach the basal ganglia?
through the corticostriate pathway to the spiny neurons in the neostriatum
Is the synapse ont he spiny neuorns excitatory or inhibitory? WHat NT?
excitatory - glutamate
Are the spiny neurons inhibitory or excitatory? What NT?
inhibitory - GABA
What are the two types of spiny neurons?
GABA/enkephalin neurons
GAMA/substance P neurons
What are the two pathways of striatum projections and which type of spiny neurons do they use?
direct pathway: GABA/SP
indirect pathway: GABA/Enk
Where do the GABA/SP spiny neurons project to in the direct pathway? (2 places)
mainly to the internal segment of the globus pallidus
also to the pars reticulata of the substantia nigra (SNr)
Where does the globus pallidus send information to?
VA/VL thalamus, then onto motor cortex
What is the purpose of the projections to the SNr?
They continue on to the thalamus and brainstem
then to the superior colliculus for eye movements
and pedunculopontin nuclei for locomotion
Where do the GABA/Enk spiny neurons project to in the indirect pathway?
the external segment of the globus pallidus
Where does the external segment of the globus pallidus project to in the indirect pathway?
the subthalamic nucleus (inhibitory)
Where does the subthalamic nucleus project to in the indirect pathway?
the internal segment of the globus pallidus
(and the substantia nigra pars reticulata)
Where does the vast majority of the excitatory input to the globus pallidus internus come from and what does that mean for motor control?
the subthalamic nuclei
since the GPi is inhibitory to the thalamus, the subthalamic nuclei therefore has most of the control over the basal ganglia output
without it, you get balismus because you lose the motor inhibition
What role does the substantia nigra compacta play?
It receives inhibitory input from the GABA/SP cells
it uses dopamine to inhibit the GABA/Enk cells via D2 receptors and activate the GABA/SP cells via D1 receptors
very important for the selection of movement for reward
Ultimately, the GPi tonically _____ the thalamus and motor funciton
inhibits
Thus, to get motor activity, you need to _____ GPi activity.
decrease
So…
the direct pathway _____ movement
and
the indirect pathway _____ movement
direct = activates movement
indirect = suppresses movement
What is dopamine’s effect on motor activity?
It increases motor activity
(inhibits the indirect pathway and activates the direct pathway)
Disruption of the basal ganglia will result in _____ movement.
involuntary
Specifically, what symptoms wil result from a subthalamic lesion?
hyperkinetic dyskinesia = ballismus
(wild exaggerated movement of contralateral limbs)
due to loss of excitatory drive to GPi - no more inhibition on the thalamus
What happens in Parkinson’s?
You have degeneration of the pigmented cells in the SNc
this means you don’t have enough dopamine
What are the 4 major clinical findings in Parkinsons?
- bradykinesia (or akinesia)
- rigidity (not spasticity)
- resting tremor (goes away when you do something)
- postural instability
What are the 4 general etiologies of Parkinson’s?
- not known for most - maybe oxidative stress?
- encephalitis lethargica (viral encephalitis)
- toxins - CO and manganese
- Head truma - think Muhammed Ali
What is the treatment for Parkinson’s?
L-DOPA
it’s a dopamine precursor that can cross the BBB
issue is it can produce hyperkinetic movements if given too much
What do you get with a lesion of the globus pallidus?
flexion dystonia/flexion posturinng (this is a hyperactivity of motor function)
this is because you’ve lost the inhibition on the thalamus from the GPi
What do you see in putamen lesions?
patients become more motoric in nature and will repeat stereotyped behaviors over and over again
What are the symptoms of a caudate lesion?
more complex and cognitive…
impulsivity
vulgarity
hypersexuality
increased appetite and thirst
What is the genetic cause of Huntington’s Chorea?
It’s an autosomal dominant CGA repeat (gain of function) on the short arm of chromosome 4.
When is the onset of Huntington’s?
25-40 years old
What are the first neurons to die in Huntington’s?
the spiny neurons of the neostriatum
especially the GABA/ENK of the indirect pathway
Eventually you lose the whole striatum and cerebral cortical neurons start to die too
What are the symptoms of Huntington’s?
- involuntary movements - chorea and athetosis (wormlike movements or dancelike movements) as the indirect pathway is affected and movement isn’t suppresed
- dementia and personality changes
- you eventually get akinesia as the direct pathway is affected when the whole striatum dies
What is our only real way of treating Huntington’s now?
give them a dopamine receptor blocker - essentially try to give them Parkinson’s disease and decrease the involuntary movement
