Motor Systems IV- Basal Ganglia Flashcards
A twenty six year old white mail develops uncontrolled INVOLUNTARY movements of limbs, body and trunk that are progressively getting worse.
He also is losing cognitive function.
His fatehr died of a similar disease but the onset was later in life w/ slower progression of the dieseae.
What is the disease?
Huntingtons
What are the 4 major components of the basal ganglia?
Neostriatum (INPUTS)
Globus pallidus (OUTPUT)
Substantia nigra
Subthalmic nucleus
What does the neostriatum consist of and what does it do?
Consists of caudate and putamen
Receives the major INPUTS
What are the neurons associated with the caudate and putamen and what NT do they use?
It it excitatory or inhibitory?
1. Spiny neurons
Receive INPUT and are primary OUTPUT
Two groups of neurons
- GABA/substance P (SP) group
- GABA/enkephalin (ENK) group
2. Aspiny neurons= interneurons
INhibitory
Afferent input to the striatum from OUTSIDE the basal ganglia comes from where?
What NT does it use?
It it excitatory or inhibitory?
Cerebral cortex to the straitum = corticostriate pathway
Originates from premotor and primary motor cortex
terminates on spiny neurons in neostriatum
NT: Glutamate
Excitatory projection
Describe the components of the DIRECT pathway projecting to the globus pallidus.
- Striatal (GABA/SP) neurons project to internal segment of Globus pallidus GPi
- Project to VA/VL of thlamus via lenticular fasciculus
- These areas project BACK to cortical areas and are the source of the corticostriate pathway (Cerebral cortex –> striatum)
Main OUTPUT projection
Describe the components of the DIRECT pathway projecting to the substantia pars reticulata.
What is the SNr used to control?
SNr- part of OUTPUT projection that ctronls eye movements and locomotion
Projects to thalamus (VA/VL)–>
Then to brainstem–>
Superior colliculus for eye movements
Peduncolopontine nuclei for locomotion
Describe the striatum projections via the INDIRECT pathway.
GABA/ENK spiniy neurons inhibit the external segment of the globous pallidus (GPe)–>
GPe inhibits (GABA) the subthalamic nucleus (STh)–>
STh excites GPI/SNr
(uses glutamate)
Source of major EXCITATORY input to GPi and SNr
Also recieves input from the cerebral cortex through the hyperdirect pathway (Glut +)
How is the SNc linked to the striatum?
What is it used for?
Striatum (GABA/SP) spiny neurons inhibits–>SNc/ SNR
SNc–> spiny neurons
Selection of movements and rewards
What are hte two effects of the SNc when it terminates on spiny neurons?
- INHIBIT GABA/ENK via D2 receptors
- EXCITE GABA/SP neurons via D1 receptors
What are the three major pathways from the cortex to striatum to GPi and what do they do?
- Direct pathway–facilitates movement
Cortex >+ striatum > - GPi–> - thalamus > + movement
- Indirect pathway–suppresses movement
Coretex > + striatum> - GPe > - STh > + GPi > - Thalamus > - movement
- Hyperdirect pathway–suppresses movement
Cortex > STh > GPi
GPi when activated is INHIBITORY to the thalamus and DECREASES motor activity.
Motor activity requires DECREASING Gpi activity.
Describe how the basal ganglia circuit is used in eye movements.
How does an increase in dopamine affect the striatum?
- Less excitation of STh on GPi
- Increase of inhibition on GPi via putamen
This leads to less GPI inhibitory output to VA/VL–>
MOTOR ACTIVITY
What do subthalamic lesions cause?
Hyperkinetic dyskinesia
- Ballismus- wild exaggerated movements of the limbs d/t loss of excitatory drive on GPi
A patient present with braykinesia, rigidity, a resting tremor and postural instability. What diesease do they have?
What is the treatment
Parkinson’s disease
Resotre dopamine using L-DOPA
This can lead to hyperkinetic movements (involuntary movements)
A lesion of the GPi would cause what symptoms?
Flexion dystonia
(sustained muscle contraction d/t an increase in motor activity)
Loss of normal tonic inhibitory activity of GPi on VA/VL–> uncontroled movements
A lesion of the putamen (part of the striate) would cause what disorders?
Motoric in nature
stereotypic behavior–repeat actions over and over
A lesion of the caudate would cause what movement disorders?
Caudate= prefrontal cortex/ pre-motor cortex/ SMA
Changes in “complex behvaiors”
Cognitive disorders:
vulgarity, impulsivity
increased apetite, polydipsia
hypersexuality
What gene is associated with Huntingtons?
AUTOSOMAL DOMINANT
abnormal gene on short arm of chromosome 4
CGA repeat–> gain of function
25-40 years old
What is the pathology of Huntingtons?
Death of spinyp neurons in neostraitum (pariculary GABA/ENK group)
Loss of cerebral cortical neurons
All of striatum eventually dies
What are the symptoms of Huntingtons?
Involuntary movements
Dementia/personality changes
akinesia (impaired voluntary movement)
How do you treat Huntingtons?
Dopamine receptor blockers
