7 - Basal Ganglia Flashcards
hypokinetic movement disorder?
too little movementq
hyperkinetic movement disorder?
too much movement, and often abnormal involuntary movements
what is the input region of the basal ganglia?
striatum
what neurons are found within the striatum?
medium spiny neurones
interneurones
what type of neurones are medium spiny neurones?
GABAergic
neuropeptides
inhibitory
where do medium spiny neurones project to and from?
project from basal ganglia to other regions
where do interneurons project?
w/i the basal ganglia
what type of neurons are interneurons?
GABAergic
cholinergic
what are the two pathways that input into the striatum?
- corticostriatal - main input
- nigrostriatal - fine tunes excitation
what type of pathway is the corticostriatal pathway?
glutamatergic
where does the corticostriatal pathway receive input from?
whole cerebral cortex
what type of pathway is the nigrostriatal pathway?
dopaminergic
where does the nigrostriatal pathway receive input from?
substansia nigra pars compacta
when dopamine and glutamate interact, what do they do?
modulate synaptic strength
which dopamine pathway is direct?
D1
which dopamine pathway is indirect?
D2
what neuropeptide is associated with the D2 pathway?
enkephalin
what neuropeptide is associated with the D1 pathway?
dynorphin
what is the basal ganglia responsible for?
fine tuning the initiation, control and termination of movements
what are the different components of the basal ganglia?
6
- putamen
- caudate
- globus pallidus internus
- globus pallidus externus
- substantia nigra
- subthalmic nucleus
the striatum refers specifically to what two components?
caudate and putamen
what are hte two pathways involving dopamine in the basal ganglia?
indirect pathway
direct pathway
how does the indirect pathway affect movement>
negative modulator of movement
how does the direct pathway affect movement?
positive modulator of movement
how does dopamine affect the direct and indirect pathways within the basal ganglia?
increased movements by activating direct pathways and inhibiting indirect pathway
outline how the direct pathway initiates movement?
- motor cortex sends excitatory signals to the striatum via glutamate
- striatum sends inhibitory signals to the GPi and SNr via GABA
- stops their resting function which is to inhibit the thalamus
- thalamus is now dis-inhibited
- thalamus sends excitatory signals to motor cortex via glutamate
- motor cortex allows movement to occur
what role does dopamine play in the direct pathway w/i the basal ganglia?
- activates stiatum by interacting with D1 receptors (excitatory)
- increases striatum’s inhibitory effect
- increases propensity towards movement
outline how the indirect pathway regulatesmovement:
- motor cortex sends excitatory signals to the striatum via glutamate
- striatum sends inhibitory signals to the GPe via GABA
- GPe sends reduced GABA signals to subthalmic nucleus
- subthalmic nucleus is dis-inhibited = sends more glutamate to GPi
- excites GPi = sends more inhibitory signals to the thalamus via GABA
- thalamus is inhibited = sends less excitatory signals to motor cortex
- no impules is sent down spinal cord = decreased movement
what role does dopamine play in the indirect pathway w/i the basal ganglia?
- binds to D2 receptors (inhibitory)
- striatal neurons have reduced inhibition
- supresses excitatory actions of subthalmic nucleus
- GPi has less inhibition on the thalamus
- increases motor cortec excitation
what type of receptor are the D1 and D2 receptors?
G coupled protein receptors
D1 and D2 are both G coupled receptors - what is their overall effect?
- activates the conversion of ATP to cAMP
- causes phosphorylation/activation of intracellular substrates
what are levels of dopamine during resting conditions?
low synaptic and extrasynaptic levels
what are dopamine levels in active movement?
phasic dopamine release
which dopamine receptors are preferential in resting conditions?
D2
which dopamine receptors are preferential in active movement/learning?
D1
how are the dopamine pathways different in parkinsons?
- relative overactivity of indirect pathways
- relative underactivity of direct pathways
what are 3 behavioural impairments in PD?
- cognitive disturbances - later dementia related to Lewy body pathology
- impulse behaviour
- depression, anxiety
impulse behaviours in PD are linked to what?
severe dopaminergic deficit in ventral striatal areas
depression and anxiety in PD are linked to what?
monoamine cell loss in brainstem
what are 4 hyperkinetic movement disorders?
- chorea
- dystonia
- myoclonus
- tic disorders
what are three hallmarks of chorea?
- rapid, random irregular movements
- flitting between various muscle groups and body parts
- motor impersistence - can’t maintain voluntary movements
what is the pathophysiology of chorea?
- relative overactivity of direct pathways - excessive movement
- underactivity of indirect pathways - no suppression of unwanted movements
what is the pathophysiology of Huntington’s disease?
- selective loss of D2 receptor-bearing indirect pathway neurones = involuntary movements
- later loss of direct pathway neurones = hypokinetic movement disorders
- loss of encephalin in indirect pathways
what DNA sequence is altered in Huntington’s disease?
expanded CAG repeats
what are the two hallmarks of Tourette’s syndrome?
- rapid, repetitive movements or vocalisations
- comorbid neuropsychiatric illness - OCD or ADHD
what is the pathophysiology of Tourette’s?
- loss of cholinergic and GABAergic striatal interneuones = reduced basal ganglia inhibition
- increased dopamine D2 receptor binding
