Basal Ganglia Flashcards
What is the basal ganglia?
Cluster of subcortical nuclei deep in the cerebral hemispheres. Largest component striatum (caudate nucleus and putamen), globus pallidus, subthalamic nucleus and substantia nigra.
What is normal action of basal ganglia?
Tonically active inhibitory output from SN pars reticulata. Suppresses inappropriate motor programs.
Temporary activation of DP releases one motor program from inhibition.
Thus the BG acts as a gate.
What is the function of the IP?
Increases the activity of output nuclei, suppressing activity in the thalamus and cortex.
What is the function of the DP?
Suppresses tonic activity of output nuclei allowing for activation of thalamus and cortex.
What do the IP and DP have?
Opposite net effects on target structures.
Describe the IP.
Striatum stimulates inhibitory axons to the GPe. Decrease activity in inhibitory axons to subthalamic nuclei, increasing activity in excitatory axons that project to the GPi, increasing inhibitory activity to thalamic nuclei.
Non-clinical evidence for function of IP.
Kravitz et al (2010). Optogenetic stimulation of striatal MSNs of IP decreased motor initiation and increased bradykinesia.
Describe the DP.
Striatum stimulates inhibitory axons to GPi, causing decreased excitatory input to thalamic nuclei. Disinhibition.
Non-clinical evidence for function of DP.
Kravitz et al (2010). Optogenetic stimulation of striatal MSNs in DP increased locomotion in mice.
Where does the nigrostriatal projection come from? What is its effect?
Substantia nigra pars compacta.
Excites DP and inhibits IP. Thus net effect of exciting the cortex by two routes.
What does effect of nigrostriatal projection explain?
Why increased dopaminergic tone is associated with increased locomotor activity. Amphetamine.
Acute administration of selective dopamine agonist apomorphine increased locomotor activity in zebrafish. Irons et al (2012).
What causes Huntington’s Disease?
A mutation in the HHG gene which leads to the accumulation the neurotoxic protein Huntingtin in the striatum, decreasing striatal output.
What evidence suggests that the output of the GPi serves to inhibit movement?
Hemiballismus (rapid, forceful and involuntary movements of the proximal limbs) associated with reduced activity in the globus pallidus: Potsuma and Lang (2003) found that it exhibited majorly decreased firing rate in the disorder, from around 70 to 40 spikes a second.
Why are IP neurons most damaged in the early stages of HD? What does this mean for early symptoms?
Most sensitive to Huntingin.
Hyperkinetic symptoms (reduced inhibition). Chorea, dance-like movements.
What symptoms may arise in late-stage HD? Why?
Bradykinesia, akinesia.
Late stage attack of DP neurons.
What causes PD?
Buildup of proteins in the brain into abnormal aggregates called Lewy bodies, which are themselves toxic to neurons in the substantia nigra.
Because the substantia nigra contains many dopaminergic projections to the striatum, PD leads to a reduction in dopaminergic input into the BG.
What suggests PD associated with increased inhibitory tone in BG?
Hypokinetic symptoms (bradykinesia, rigidity).
Treated with L-DOPA, dopamine net excites.
What is Tourette’s Syndrome? What evidence suggests BG plays role?
Rapid, involuntary repetetive movements/vocalisations (tics).
Tarsy et al (1978) animal model, rats, local disinhibition of striatum picrotoxin (GABAa antagonist) induced appearance of motor tics.
What is focal dystonia? How may it be related to the BG?
Involuntary muscle contractions in a specific part of the body.
Hyperactivity of DP implicated. Simonyan et al (2017).
How many the BG play a role in learning what motor actions are rewarding?
SNc recordings show respond to unexpected reward and decrease when failure to receive.
Dopaminergic firing may be involved in tuning relative balance of IP/DP activity towards programs that produce rewarding outcomes.
