MOVEMENT DISORDERS Flashcards
what is the lentiform nucleus made up of?
putamen and globus pallidus
what is the corpus striatum made up of?
neostriatum and palleostriatum
what are the three main functions of the basal ganglia?
control movement
prevent involuntary movement
control behaviour
what is the neostriatum made up of?
caudate nucleus and putamen
also just referred to as the striatum
the palleostriatum contains which structure?
globus pallidus
the indirect pathway is regulated by which dopaminergic receptor?
D2
the direct pathway is regulated by which dopaminergic receptor?
D1
what is the function of the direct pathway?
stimulate voluntary movement
what is the function of the indirect pathway?
inhibit involuntary movement
in the direct pathway, what is the resting function of the globus pallidus interna?
inhibit the thalamus using GABA
which structures are involved in the indirect pathway but not in the direct pathway?
sub thalamic nucleus
globus pallidus externa
the resting function of the globus pallidus interna is…
inhibition of the thalamus- hence preventing involuntary movement
where is dopamine released from in both the direct and indirect pathways?
substantia nigra PARS COMPACTA
what is the function of the substantia nigra pars reticulata in the direct pathway?
at rest, SNPret inhibits the thalamus
when inhibited by GABA from striatum, the ‘brake’ on the thalamus is lifted
SAME FUNCTION AS GPINTERNA
which pathway is associated with an INCREASE in GABA inhibition from striatum?
They both are
which pathway is associated with a DECREASE in GABA inhibition from the GP externa?
INDIRECT pathway
what is the effect of dopamine on both the direct and indirect pathways?
overall net increase in movement by ACTIVATION of the direct pathway and INHIBITION of the INDIRECT pathway
what is the effect of D2 receptor activation on the globus pallidus interna?
INCREASED glutamate ++++
indirect pathway
what is the effect of D1 receptor activation on the globus pallidus interna?
INCREASED GABA ++++
direct pathway
in the indirect pathway, what is the resting function of the globus pallidus externa?
INDIRECT inhibition of the GP interna via sub thalamic nuclei
what are medium spiny neurones? What receptors do they express?
GABAergic inhibitory neurones that make up 96% of striatum neurone population. Either have D1 or D2 phenotype
what neuropeptide is associated with the D1 pathway?
Dynorphin
what neuropeptide is associated with the D2 pathway?
Enkephalin
tonic Da release from SN favours activation of which pathway?
D2 - increased inhibition e.g. at rest
phasic dopamine release from SN favours activation of which pathway?
D1 - increased activation e.g. when active
what are the 4 cardinal symptoms of PD?
bradykinesia
postural instability
resting tremor
rigidity
what are the craniofacial symptoms of PD?
hypomimia (lack of facial expression)
dysphagia (incorrect speech)
hypophonia (quiet voice)
what gait is associated with parkinsons?
Shuffling gait aka. parkinsonian gait
shuffling
stooped posture
freezing - inability to move forwards
what are the two types of bradykinesia?
akinesia
hypokinesia
what is akinesia?
inability to perform spontaneous movement
what is hypokinesia?
in addition to being slow, movements are also smaller than desired e.g. micrographia
what are the non-motor features of parkinsons?
pain
anosmia
constipation/GI problems
REM sleep behaviour disorder
what are central pattern generators?
neural circuits in the brainstem that control subconscious movements e.g. walking and breathing
lack of dopamine inhibits CPGs and causes bradykinesia
what changes are seen in muscle fibres types in PD patients?
increased inhibition of type Ib fibres (golgi tendon stretch)
increased activation of type II fibres (these control muscle fibres when static)
what drug targets the glu neurones between the thalamus - cortex - basal ganglia?
amantadine (NMDA receptor antagonist)
reduces dyskinesia by 40%
what drug is given subcutaneously via infusion to administer tonic dopamine?
apomorphine
what is neuroleptic malignant syndrome?
fever, confusion, rigidity and tachycardia following rapid withdrawal of PD meds
what is the cause of dyskinesia in parkinsons?
Glutamate excess caused by increased dopamine (due to pulsatile release etc.)
What is chorea disorder?
hyperkinetic disrder that is opposite to PD
underactive indirect pathway
overactive indirect pathway
uncontrolled movement
what is Huntingdons disease?
autosomal dominant CAG repeats
selective D2 neurone death, followed by direct pathway loss as disease progresses
what is tourettes syndrome?
caused by loss of basal ganglia interneurones in the striatum (both GABA and Ach)
