Basal ganglia and parkinsons Flashcards
what areas make up the basal ganglia
neostriatum
paleostriatum
subthalamic nucleus
substantia nigra
what is the basal ganglia
deep cerebral nuclei
primarily for motor control, also motor learning, executive functions, behaviours, emotions
what is the neostriatum
caudate nucleus
putamen
what is the paleostriatum
globus pallidus
what is special about the substantia nigra
filled with melanin
pars reticulata- GABAergic
pars compacta- dopaminergic
produce dopamine (dopaminergic neurons)
what is the function of the basal ganglia
smooth movement- basic patterns of movement
switching behaviour
reward systems
closely linked to thalamus, cortex and limbic system
what does the direct pathway vs indirect pathway of the basal ganglia motor look do
simple terms
direct- stimulate movement
indirect- inhibition of movement EXTRA STEP
how does the motor loop work
cortex
corpus striatum
basal ganglia-> thalamus
thalamus to cortex
what is the corpus striatum
caudate nucleus
putamen
globus pallidum
what is extra in the indirect loop
globus pallidus lateral is inhibited by neostriatum
therefore subthalamic nucleus is not inhibited and can stimulate the globus pallidus (medial) to inhibit the thalamus
what happens when you want to cause a movement to occur
cortex sends simulating input
stimulate inhibitory neurons
inhibit release of inhibitory NT from globus pallidus (medial)
removing inhibition of thalamus so thalamus is stimulated
therefore there is a POSITIVE STIMULATORY SIGNAL back to the cortex= MOVEMENT
where does dopamine come from
substantia nigra PARS COMPACTA
it tips the balance between indirect and direct pathway to cause movement.
two different receptors found in the neostriatum (caudate nucleus and putamen)
substantia nigra feeds into niastriatum
what is the pathway of the indirect path
cortex
neostriatum
globus pallidus (lateral)
subthalamus
globus pallidus (medial)
thalamus
extra step causes inhibitory signal coming out- inhibit thalamus and therefore inhibit movement.
what is the inhibitory neurotransmitter released by the neostriatum
GABA
what NT does the cortex release (excitatory), which is also released b the subthalamus in the indirect pathway
glutamate
what are the different dopamine receptors in the direct and indirect pathways
direct- D1 receptors– release of dopamine attaches and stimulation of direct pathway
indirect- D2 receptors
therefore tips the balance
what are some clinical problems found in the basal ganglia
PARKINSONS
HUNTINGTONS
HEMIBALLISM
WILSON’S DISEASE
describe clinical features of parkinsons disease
tremor at rest
rigidity (limbs>axial)
bradykinesia- slowness to INITIATE MOVEMENT
asymmetry
lossrighting reflex
30% cognitive decline
hypomimia (lack of facial expression)
glabellar tap
quiet speech
micrographia
pill rolling
trunk tilting to maintain balance
akinesia
describe the pathophysiology of the basal ganglia in parkinsons disease
there is a degeneration of dopaminergic neurons of substantia nigra PARS COMPACTA
therefore loss of dopamine
no dopamine input
direct pathway not stimulated as much
no inhibition of the globus pallidus
therefore inhibitory signal to thalamus is greater
inhibits thalamus so signal to frontal cortex is reduced (movement occurs much slower)
also indirect pathway is no longer inhibited
strong inhibitory signal
etc.
stimulating globus pallidus medial which is inhibitory!- no inhibition coming from neostriatum
slow initiation of movement
describe huntington’s disease
symptoms,
what is affected
autosomal dominant
CAG triplet repeat disease (>40 repeats) this causes mutant huntintin protein accumulates– becomes toxic and BREAKS DOWN CAUDATE NUCLEUS
causes CHOREA, BEHAVIOURAL DISORDERS, DEMENTIA
caudate nucleus wasting
hyperkinetc- forceful movements
hypotonia
what is the triplet code affected in huntingtons
CAG triplet repeat
describe the pathophysiology of the basal ganglia involved in huntingtons disease
dopamine not affected
neostriatum affected
specifically targets the INDIRECT pathway
-reduced outflow of inhibitory signal going to globus pallidus, inhibit signal from GP increased
-substantial inhibition of the subthalamus
-no input in GP medial
-reduced inhibitory outflow
-remove inhibition from thalamus
-powerful signal back to cortex
FORCEFUL MOVEMENTS
by knocking out smoothing of movement done by indirect pathway
describe wilsons disease
abnormal recessive
abnormal copper accumultion
HEPATO-LENTICULAR DEGENERATION (liver and brain)
dystonia, ataxia, subcortical dementia
involuntary movements
copper transport protein abnormality
low serum copper and caeruloplasmin
KAYSER-FLEISHER RINGS
PENICILLAMINE treatment
name an autosomal dominant an autosomal recessive disorder involving the brain
autosomal dominant- huntingtons
autosomal recessive- wilsons
what are some treatments for parkinsons
levadopa (precursor)
with either:
-carbidopa
-benserazide
OR
-entacapone
-tolcapone
D1/D2 agoinsts
describe side effects of levodopa
dyskinesia- may appear within 2 years
affect face and limbs
rapid FLUCTUATIONS
eg. hypokinesia, rigidity may worsen then improve
reflects fluctuating receptor dynamics
limited in effectiveness with time as neurodegeneration progresses
what does the combination of levodopa with a dopa decarboxylase inhibitor allow
it allows for the dose to be lower
reduces peripheral system side effects (nausea, hypotension)
what is the role of MAO inhibitors
protect dopamine from extraneuronal degradation
with levadopa it relieves symptoms and prolong life
what is amantadine
what does it do and why is it not commonly used
antiviral drug
increases dopamine release- primarily responsible for its therapeutic effect
less effective than levadopa and bromocriptine
action declines with time
name some acetylcholine antagonists and why they can be used
trihexyphenidyl (benzhexol)
orphenadrine
procyclidine
musc ach receptors exert inhibitory effect on dopaminergic nerves–lack of dopamine
what other treatments are there that dont involve medications
neural transplantation
brain stimulation
what is hemiballism and what symptoms does it give
subthalamic deficit
hyperkinetic
violent, involuntary movements
