Case 7 - Basal Ganglia Lecture Flashcards
what is meant by hypokinetic
too little movement
what is meant by hyperkinetic
too much movement
often abnormal involuntary movements
what can both of these be caused by
basal ganglia dysfunction
what is the input nucleus
the striatum made up of the caudate and putamen
what is the D1 pathway
this pathway projects directly to the globus pallius media - contains GABA which is the main inhibitory neurotransmitter and that projects directly to the GPm D1 dopamine receptors
what are the output regions of the basal ganglia
the globus pallidus media along with the substantia nigra pars reticulate
where does the indirect pathway project
to the GPl and then to the output region, the medial globus pallidus via another GABA transmission pathway to the sub thalamic nucleus which then projects back using glutamate to the medial globes pallidus
features of the striatum
comprises the caudate and putamen
input region of the basal ganglia
what are medial spiny neurones
dendritic spines
what do medium spiny neurones do
vastly increase surface area and are 96% of striata neurones
medium spiny neurones are ……..ergic
GABAergic ± neuropeptides
what are internueones
don’t project outside of the striatum
features of interneurones
GABAergic
Cholinergic (large aspiny neurones)
where does striatal input come form
corticostriatal pathway and nigrostriatal pathway
features of the corticostriatal pathway
glutamaterguc
inout from the whole cerebral cortex
features of the nigrostrital pathway
dopaminergic
from substantia nigra pars compatacta
projects to the striatum
interaction of dopamine and glutamate which controls the level of activity in the striatum
dopamine regulates and fine tunes the output of the basal ganglia
what do dopamine and glutamate interact to do
modulate synaptic strength
what are the neuropeptides in the direct pathway
dynorphin and substance P
what are the neuropeptides in the indirect pathway
enkephalin
what is the dynorphin precursor
PPE-B
what is the enkephalin precursor
PPE-A
where does the D1 receptor mainly act
on g-alpha-s subunits - excitatory and activates adenyl cyclase which leads to cAMP formation
where does the D2 receptor mainly act
on inhibitory G protein subunits which inhibits adenylyl cyclase and leads to less activation of cAMP
diagram of basal ganglia organisation
what does the D2 pathway involve
The suppression of unwanted movements
what does the D1 pathway involve
the facilitation of wanted movements
what is the action of dopamine in resting conditions
what are the actions of dopamine in active movement
What is the hyper direct pathway
additional role in inhibitory control
parallel loops subserving different functions
dorsolateral to ventromedial gradient in terms of function
where is the hyper direct pathway from
the cortex to the STN
what happens if there is a loss of dopamine in the direct pathway
reduced excitation
what happens if there is a loss of dopamine in the indirect pathway
reduced inhibition
diagram demonstrating the basal ganglia in Parkinson
is there an increase or decrease of enkephalin in parkinsons
increase in enkephalin
is there an increase or decrease of dynorphin in parkinsons
decreased production of dynrophin
what is the net result
is there is less inhibition of the output regions of the basal ganglia via the direct pathway and there is too much excitation via the indirect pathway
what does this therefore lead to
the output from the basal ganglia is increased - increased inhibition of the brainstem and spinal cord and increased inhibition of the motor part of the thalamus
this leads to reduced excitatory output from the thalamus and reduced excitation of the cortex which leads to less movement
what is the pathophysiology of Parkinsonism
relative overactivity of the indirect pathway
suppression of movement which leads to bradykinesia and rigidity
impaired motor learning - loss of LTP
subthalamic overactivity - lesions of STN alleviates experimental Parkinsonism and effects of lesion surgery?
what are the cognitive disturbances linked too in PD
changes in dopamine handling in basal ganglia loops
later dementia related to cortical Lewy body pathology
impulsive behaviour in PD:n
pathological gambling, hypersexuality and compulsive eating
linked to more severe dopaminergic deficit in ventral (limbic) striata areas
depression and anxiety in PD
related to monoamine cell loss in the brainstem
dopamine agonists may improve depression in PD
what are hyperkinetic choreiform disorders
huntinngtons disease
Levodopa induced dyskinesia
dystonia
tic disorders
what is Chorea
rapid, multifocal irregular movements
flitting between various muscle groups and body parts
motor impersistence
what is the pathophysiology of chorea
imbalance between direct and indirect pathways
relative overactivity of direct pathway - excessive movement
under activity of indirect pathway - no suppression of unwanted movement
what is Huntington’s disease
expanded CAG repeats in Huntington Gene (chromosome 4p16.3)
complete penetrance with over 40 repeats
anticipation, greater expansion with male transmission
what is the pathophysiology of Huntingtons
selective loss of D2 receptor bearing indirect pathway neurones –> involuntary movements
later loss of direct pathway neurones –> hypokenetic movement disorder
what is the cortical pathology in HD
loss of neurones in layers V and VI
what is the striatal pathology
degeneration in caudate and indirect pathway D2 receptor bearing MSNs
diagram for the basal ganglia in HD
what is Tourette syndrome
tic disorder, usually onset age of less than 20
rapid, repetitive stereotyped movements or vocalisations
frequent comorbin neuropsychiatric illness
what is the pathophysiology of touettes
loss of cholinergic and GABAergic striata interneurones
increased striata dopamine D2 receptor binding in patients with TS compared to controls
what are the therapies used in tic disorders
antidopaminergic therapy - tetrabenzine
antipsychotic agents - haloperidol, sulphide (block D2 receptor)
alpha receptor agonists - clonidine
