The Basal Ganglia Flashcards
What are the basal ganglia?
a group of nuclei of varied origin that act as a functional unit
Where are nuclei of telencephalic origin?
basal to the overlying cerebral cortex
What is the striatum?
a cluster of interconnected nuclei that form part of the basal ganglia involved in decision making functions
What are the 3 nuclei of the corpus striatum?
- caudate nucleus
- lentiform nucleus
- nucleus accumbens
What is the structure of the caudate nucleus?
C-shaped, following the curve of the lateral ventricle
What is the lentiform nucleus made up of?
- internal and external globus pallidus
- putamen
What is the input portion of the basal ganglia?
the caudate-putamen connections which receive projections from the overlying cerebral cortex
Where is the subthalamic nucleus and what is its origin?
inferior to the thalamus of diencephalic origin
Where is the substantia nigra and what is its origin?
in the midbrain of mesencephalic origin
What does the substantia nigra consist of?
- substantia nigra pars compacta
- substantia nigra pars reticulata
What neurons use dopamine as a neurotransmitter?
those that contain a lot of neuromelanin
What are the 5 functional entities of the basal ganglia and what type of neurons do they have?
- corpus striatum (GABAergic neurons)
- GPe (GABAergic neurons)
- STN (glutamatergic neurons)
- GPi and SNr (GABAergic neurons)
- SNc (dopaminergic neurons)
What is the major afferent projection received by the striatum?
glutamatergic excitatory input from the cerebral cortex
What are the major output nuclei of the basal ganglia?
GPi and SNr
What do the GPi and SNr exert their inhibitory influence on?
the excitatory neurons located in the ventral tier thalamic nuclei
What are the 2 major projection systems between the input and output structures of the basal ganglia?
direct and indirect pathways arising from separate neuronal populations in the striatum
Describe the direct pathway of the basal ganglia
- cortical inputs from motor areas excite striatal neurons that contain substance P and dynorphin
- GABAergic projections monosynaptically inhibit the GPi-SNr which decreases inhibition of the thalamus
- this allows thalamocortical circuits to become more active, facilitating the initiation of voluntary movements
Describe the indirect pathway of the basal ganglia
- cortical inputs from motor areas excite striatal neurons that contain substance P and enkephalin
- GABAergic projections inhibit the GPe which decreases inhibition of the STN
- activation of the STN excites the GPi and SNr which increases inhibition of the thalamus, resulting in suppression of unwanted or inappropriate movements
What does dopamine do at the striatal level?
facilitate transmission along the direct pathway but inhibit transmission along the indirect pathway
What do dopamine receptors D1 and D2 mediate respectively?
- D1 = dopamine facilitating transmission along direct pathway
- D2 = dopamine inhibiting transmission along indirect pathway
What is released from inhibition in hyperkinetic disorders?
SNr and GPi
How do hyperkinetic disorders arise?
inhibitory output to the thalamus is increased and thalamic input to the cortex is decreased
What causes PD?
degeneration of dopaminergic neurons of the SNc
What are seen in SNc neurons?
Lewy bodies
What are the main risk factors of PD?
- age
- genetic predisposition
- environmental causes
What is the pathology of PD?
- mitochondrial damage
- free radicals
- proteasome dysfunction
What are signs of PD?
- resting tremor
- rigidity and stiffness
- bradykinesia or hypokinesia
- postural inability
What are pharmacotherapies of PD?
- dopamine agonists to replace lost dopamine
- levadopa
- co-administration of carbidopa
- MAO-B inhibitors that slow down dopamine breakdown
What is levadopa?
dopamine precursor that crosses the blood-brain barrier
Give an example of surgical treatment of PD
deep brain stimulation that inhibits STN and related thalamic nuclei
What do drugs of abuse do?
increase the extracellular concentration of dopamine in the nucleus accumbens
Where do the dopaminergic neurons of the VTA project?
the nucleus accumbens
What does the ability of drugs of abuse to induce changes in dopamine concentration result in?
overactivation of the neuronal processes that highlight saliency
What does addiction result from?
the repeated perturbation of reward circuits due to marked dopamine increases followed by dopamine decreases
What do drug-addicted subjects show decreases in?
number of dopamine D2 receptors
What does decreased dopamine sensitivity lead to?
decrease in interest in ordinary, day-to-day environmental stimuli
