Basal Ganglia and Movement Disorders Flashcards
What are the 4 structures of the basal ganglia?
- substantia nigra
- striatum
- globus pallidus
- subthalamic nuclei
Which part of the substantia nigra produces dopamine?
pars compacta (SNpc)
Where are medium spiny stellate neurons in the basal ganglia?
striosome, matrix
What are the input structures of the basal ganglia? What do they receive direct projections from?
striatum, also subthalamic nuclei (via hyperdirect path)
cerebral cortex
What are the output structures of the basal ganglia? What do they project to?
globus pallidus internal segment (GPi), substantia nigra pars reticula (SNpr)
thalamus (which projects back to cortex)
What are the intermediate structures of the basal ganglia? What do they modulate?
SNpc, STN
modulate activity of input and output structures
What does the direct pathway disinhibit? What is the effect on cortical activity?
disinhibits the thalamic output neuron, which excites the cortex
What does the indirect pathway disinhibit? What is the effect on cortical activity?
disinhibits the STN neuron, which excites the GPi brake
decreases thalamic feedback to cortex, inhibitory
Is the output layer cell (GPi) always inhibitory to the thalamus?
yes
What is the effect of the indirect pathway on the brake? on thalamic neurons?
ramps up the brake, inhibits excitatory thalamic neurons
What is the effect of the direct pathway on the brake? on thalamic neurons?
inhibits the brake, excites the excitatory thalamic neurons
What does the STN neuron receive input from?
GPe neuron in indirect path, direct projection from cortex
both have the end effect of exciting the STN neuron to ramp up the brake
How does dopamine affect the direct pathway?
acts on excitatory D1 receptors to ramp up the direct path to turn off the brake
How does dopamine affect the indirect pathway?
acts on inhibitory D2 receptors to turn off the indirect path to turn off the brake
What shuts off the indirect path and activates the direct path? How does it do two separate effects?
dopamine through D1 and D2 receptors
What are GP neurons involved in nonmotor loops involved in? Where are they located in the GP? What area of cortex are the related to?
short term and working memory, located in dorsomedial GP, receive input from and project back to prefrontal cortex
What are GP neurons involved in motor loops involved in? Where are they located in GP? What area of cortex are they related to?
motor tracking, located in ventral GP, receive input from and project back to motor areas
Where is activity in GP for visually guided tracking task?
track neurons are ventral
Where is activity in GP for remembered sequence tasks?
REM (remember) neurons are dorsomedial
receive input from SMA (associated with sequential motor performance) and prefrontal area
What area is activated in Tower of London task?
dorsomedial GP because it involves higher order control, planning and cognition
What is the hyperdirect path?
from cortex to STN, ramps up brake
What is the striosomal path? What does it cause the release of?
from cortex to MSSNs in striatum that project to SNpc (don’t participate in direct or indirect path)
causes release of DA from reward cortical areas
What neurons are involved in habit learning?
cholinergic TANs (tonically active neurons), dopaminergic neurons and MSSNs in striatum
When are SNpc and TAN activated by motor cues?
only when the movement is motivated by rewards (reward based shaping of neuronal activity)
How do TANs participate in reward based shaping of neuronal activity?
Ach release increases release of DA whenever dopaminergic neurons are firing (since TANs are tonically active will fire with the DA neurons to get conditioned)
What is hyperkinetic dysfunction of basal ganglia caused by?
abnormally low levels of basal ganglia output, brake is abnormally turned off
What are some hyperkinetic disorders?
huntingtons, syndenham’s chorea, hemiballism
What is hypokinetic dysfunction of basal ganglia caused by?
excessive levels of basal ganglia output, brake is abnormally turned on
What is the major hypokinetic disorder? What causes it? What are the symptoms?
Parkinsons
loss of SNpc DA-producing cells
akinesia, bradykinesia, resting tremor, deadpan face
What is chorea?
dance-like, quick jerky purposeless movements
primarily involves distal muscles of extremities
What is Sydenham’s chorea?
autoimmune reaction to group A strep
autoantibodies react with striatum and attack cells in indirect path
What pathway does Huntington’s target?
indirect path, cells in this path express different neuropeptides suscpetible to the mutation
What are the higher order/extra motor consequences of basal ganglia damage in Huntingtons? sydendham’s chorea? parkinsons?
huntingtons- cognitive deficits, dementia
sydenham’s chorea- emotional, behavioral deficits, OCD
parkinsons- dementia in advanced stages
Why does carbon monoxide poisoning affect basal ganglia?
big metabolic sink because of tonically active cells, causes pathology because basal ganglia isn’t getting oxygen
How do wasp stings affect basal ganglia?
due to autoantibodies attacking basal ganglia
How do you treat Huntingtons?
block excessive action of direct path with anti-DA drugs
How do you treat Syndenham’s chorea?
antibiotics for the strep, immunosuppressants against the autoantibodies, plasmapheresis
How do you treat Parkinson’s with meds (4)?
L-DOPA (because DA is too big to cross BBB and will have peripheral effects)
dopamimetics, MAO-B inhibitors to prevent DA degeneration, anticholinergics to dampen unregulated DA release to help tremor
What are side effects of LDOPA?
dyskinesias (increased drive to primary motor cortex), hallucinations (increased drive to TE) from overexcitation of thalamus
How do you treat Parkinson’s surgically?
lesion GPi or VL thalamus, if brake is overactive destroy the brake
put DA-producing cells back in (fetal nigral tissue)
deep brain stimulation to pacemake STN to force normal rhythm of discharge
