The Basal Ganglia Flashcards
What is this?
Collection of subcortical nuclei with the forebrain
What is this important for?
Movement - adjust the force of our movements
Where does it receive input from?
All areas of the neocortex - motor cortex and the limbic cortex
Project back to the motor cortex
Allows us to adjust the force of our movements
What is the volume hypothesis?
The internal globus pallidus acts like a volume dial and projects to the thalamus to the motor cortex
What are the two pathways in the basil ganglia?
Direct - inhibitory effect of Gpi: too much activity leads to overactivity in the thalamus and amplified force of movement. When you inhibit the inhibitory, get disinhibition, more force
Indirect - excitatory effect of Gpi: too much activity leads to under activity in the thalamus and reduced force of movement. Inhibits the globes pallidus, releases more GABA, reduces outcome
What does damage to the basal ganglia cause?
Hyperkinetic symptom
Hypokinetic symptom
What is hyperkinetic symptom?
Symptoms of brain damage that result in excessive involuntary movements, as seen as in Huntington’s chorea or hemiballism
What is hypokinetic symptom?
Symptom of brain damage that result in a paucity of movement, as seen in Parkinsons disease - won’t see movement, more rigid
What is Huntington’s chorea?
Genetic disorder, affects muscle coordination
Symptoms: excessive spontaneous movements, irregularly timed, randomly distributed, and abrupt in character
What is Huntington’s chorea caused by?
Atrophy of caudate nucleus and putamen (degeneration of indirect pathway neurons, direct pathway spared) - don’t get inhibition, so get random movements
What drugs reduce Huntington’s chorea?
Antipsychotics - that block dopamine transmission - so reduce the amounts of movements
Anxiolytic GABAergic drugs - that increase inhibitory transmission
What is hemiballism?
Caused by stroke to the sub thalamic nucleus - indirect pathway not working, so inhibitory not working, get too much movement
results in involuntary, fast, movements
Treatment - clozapine - dopamine blocker
What is Parkinson’s disease?
Slowly progressive disorder than affects movement, muscle control and balance
Symptoms: slowness of movement, resting tremor, stiffness of muscles, ‘gait’: small shuffling of steps
What is Parkinson’s disease caused by?
Loss of substantia nigra that sends dopamine projections to putamen that controls movement and coordination - degeneration of neurons
can be chemically induced by the toxin ‘MPTP’, thought it was heroin, woke up with Parkinson’s - use it in animals to mimic symptoms to help drugs
How can you treat Parkinson’s?
L-dopa - increases dopamine
What does dopamine increase?
Dopamine normally increases activity in the direct pathway (D1R expressing) neurons, and decreases activity in the indirect pathway (D2R expressing neurons)
What does MPTP treated to monkeys show?
Show that there is overactivity in the indirect pathway and under activity in the direct pathway - the turning up system (direct pathway) is less active, and the turning down system (indirect pathway) is more active
Globus pallidus internal can be lesioned to treat symptoms of Pd
How can you induce parkinsonian symptoms?
Following dopamine-projection lesions in striatum
Use 6-hydroxydopamine (6-OHDA) to lesion DA terminals in striatum
Use virus to express light sensitive ‘channelrhodopsin’ in only D1R-expressing neurons (direct pathway) in lesioned area
Optogenetic activation of D1R-expressing striatal neurons by shining blue light into striatum
Improvement in fine movement, decreased freezing, increased locomotor activity - activating D1, restored the symptoms
