PBL 8 - Parkinson's and Basal Ganglia Flashcards
Draw a flow chart to show the connections between the basal ganglia. Include the direct pathway and indirect pathway.
See “Motor Control” poster.
Draw and label the basal ganglia in a coronal section.
See “Basal Ganglia” poster.
Draw and label the basal ganglia in a transverse section.
See “Basal Ganglia” poster.
How big is the thalamus?
Length: 3cm
Height: 2cm
Width: 2.5cm
What is the blood supply of the thalamus?
Branches of the posterior cerebral artery
- Posterior communicating artery
- Paramedian thalamic-subthalamic arteries
- Inferolateral arteries
- Posterior medial/lateral choroidal arteries
Anatomical variant - artery of Percheron
Single artery branching from the posterior cerebral artery
What are the 2 parts of the substantia nigra?
Pars compacta
Pars reticulata
Describe the direct pathway of the motor loop.
- Cerebral cortex activates the putamen
- The putamen sends inhibitory signals to the globus pallidus (internal) and substantia nigra (reticulata) – neurotransmitter: GABA
a. Normally, the GPi and SNr would inhibit the thalamus – neurotransmitter: GABA - Therefore, when inhibited by the putamen, this allows the thalamus to be activated
- The thalamus sends excitatory signals to the cerebral cortex
- The cerebral cortex then sends excitatory signals via the descending motor pathways to control motor neurons
a. This causes movement
Describe the indirect pathway of the motor loop.
- Cerebral cortex activates the putamen
- The putamen sends inhibitory signals to the globus pallidus (external) – neurotransmitter: GABA
a. Normally, the GPe would inhibit the GPi and SNr, thus allowing the thalamus to be activated, consequently allowing cerebral activation of motor neurons (and therefore movement) - Therefore, when inhibited by the putamen, the GP (external) allows the GP (internal) and SN (reticulata) to be activated
a. This causes inhibition of the thalamus
b. This means that the thalamus does not stimulate the cerebral cortex
c. This means that there is no stimulation of motor neurons
d. Therefore, there is no movement - Role of subthalamic nuclei in the indirect pathway:
a. Activation of the globus pallidus (external) inhibits the subthalamic nucleus
b. Normally, the subthalamic nucleus would send excitatory signals to the GP (internal) and SN (reticulata), thus inhibiting the thalamus
c. Therefore, when inhibited by the GP (external), the subthalamic nucleus stops the GP (internal) and SN (reticulata)
- –This allows activation of the thalamus, therefore causing movement
Describe the role of the substantia nigra in the direct and indirect pathways.
Substantia nigra produces dopamine
Effect on the direct pathway:
- Dopamine produced by the SN (compacta) acts on the D1 and D5 receptors of the putamen
- This causes excitation of the direct pathway, therefore inhibiting the GP (internal) and SN (reticulata)
- Therefore, the thalamus is activated and causes movement
Effect on the indirect pathway:
- Dopamine produced by the SN (compacta) acts on the D2-D4 receptors of the putamen
- This causes inhibition of the indirect pathway, therefore activating the GP (external)
- This allows inhibition of the GP (internal) and SN (reticulata)
- This allows activation of the thalamus and causes movement
How does the spinal cord control movement?
Central pattern generators (CPGs)
Function: produce rhythmic motor outputs (movements) without sensory feedback or descending commands from the brain
Example: walking
- CPG creates alternating activity in flexor/extensor muscles via two sets of pattern generating neurons into the legs
- Reciprocal inhibitory connections between these sets of pattern generating neurons co-ordinate their activity, so that there is alternating activity
List the different processes involved in controlling movement.
- Control of movement in the cerebral cortex
a. Primary motor cortex
b. Premotor area
c. Supplementary motor area
d. Somatosensory area - Initiation of movement via the motor loop in the basal ganglia
- Segmental connections to motor neurons in the spinal cord
a. Reflexes - Intrinsic spinal cord control of movement
a. Central pattern generators
Describe the process of catecholamine synthesis.
- Phenylalanine (an essential amino acid) is converted to tyrosine via phenylalanine hydroxylase (mostly in the liver)
a. Cofactors needed for reaction:
- –Tetrahydrobiopterin
- –Molecular oxygen (O2) - Tyrosine is converted to DOPA (or L-DOPA) via tyrosine hydroxylase
a. Cofactors needed for reaction:
- –Tetrahydrobiopterin
- –Iron (Fe2+) - DOPA is converted to dopamine via aromatic amino acid decarboxylase
a. Cofactors needed for reaction:
- –Pyridoxal phosphate
b. By products: CO2 - Dopamine is transported into synaptic vesicles via the vesicular monoamine transporter (VMAT)
- In the vesicles, dopamine is converted to noradrenaline via dopamine-β-hydroxylase
a. Cofactors needed for reaction:
- –O2
- –L-ascorbic acid - Noradrenaline is converted to adrenaline via phenylethanolamine N-methyltransferase
a. Cofactors needed for reaction:
- –S-adenyosyl-L-methionine - Influx of Ca2+ into the neuron will then cause emptying of these vesicles into the synaptic cleft, causing AP transmission
What is the rate limiting enzyme in dopamine synthesis?
Tyrosine hydroxylase
How is tyrosine hydroxylase activity regulated?
- Phosphorylation by kinases
- Dephosphorylation
- Negative feedback by dopamine
- Oxidation by nitrates
- Formation of protein complexes
Describe the inactivation mechanism for dopamine.
- Reuptake via dopamine transporters
- Enzymatic breakdown
a. Monoamine oxidase (MAO-A and MAO-B)
b. Catechol-O-methyl transferase (COMT)
c. Aldehyde dehydrogenase - Diffusion into the circulation
a. Destroyed in liver by MAO and COMT
