L7 - Dopamine and Deep Brain Stimulation Flashcards
Where is dopamine found?
- brain
- PNS
- kidneys
- pancreas
- digestive system
What is dopamine?
A neurotransmitter which plays a key role in movement, cognition, pleasure and motivation.
Stimulation of the reward system at the same time as a behaviour does what?
Reinforces the behaviour - i.e. drives addiction to abusive drugs, or chocolate, etc.
Describe the pattern of dopamine in PD.
Full level of dopamine at the pre-manifest stage, lower level during the prodromal stage and extremely low during the fully symptomatic, manifest stage.
What does the nigrostriatal pathway connect?
Connects the substantia nigra pars compacta (SNpc) to the dorsal striatum (caudate nucleus and putamen)
What is the nigrostriatal pathway associated with?
Motor control
Why are dopaminergic neurons in the substantia nigra named ‘black body’?
The neurons there are darkly pigmented with melanin.
What does PD result from?
The selective loss of striatal neurons in the direct pathway. The balance between the pathways therefore becomes tipped in favour of the indirect pathway.
Results in loss of movement.
What does HD result from?
Selective loss of striatal neurons in the indirect pathway. The balance between the pathways therefore becomes tipped in favour of the direct pathway.
Results in excessive movement.
What does hemiballismus result from?
Lesions of the subthalamic nucleus itself, usually resulting from strokes.
Excessive movement.
What are the two cardinal symptoms of PD present in every observed patient? What is the 3rd cardinal symptom, where occasionally it is not present?
Bradykinesia and rigidity
Often resting tremor (4-6Hz), but some patients do not have a tremor at all.
What are some of the supportive prospective criteria for the definite diagnosis of PD?
3 or more of:
- unilateral onset
- rest tremor present
- progressive
- excellent response (70-100%) to levodopa
- severe levodopa-induced chorea
- clinical course of 10 years or more
What does GPi stand for?
Globus palliadus internal
What does SNr stand for?
Substantia nigra
What does GPe stand for?
Globus pallidus external
What does STN stand for?
Subthalamic nucleus
Describe basal ganglia motor circuits in normal states. Compare the difference in PD states
Direct pathway:
- motor cortex excites putamen.
- putamen has greater inhibitory effect on GPi/SNr
- GPi/SNr exerts less inhibitory effect (so has an overall excitatory effect) on thalamus
- Increased excitation of the motor cortex by the thalamus (more movement)
Indirect:
- motor cortex excites putamen
- putamen has greater inhibitory effect on GPe
- GPe has less inhibitory effect on the STN
- STN has greater excitatory effect on GPi/SNr
- GPi/SNr has greater inhibitory effect on the thalamus
- less excitation of the motor cortex by the thalamus (less movement)
In PD, there is less excitement of the putamen by the motor cortex, leading to a more overactive GPi and therefore less excitation of the motor cortex by the thalamus.
What would occur in a pallidotomy, and what would this help?
Neurosurgical procedure where the GPi is burned/lesioned.
GPi is an output structure of the indirect pathway which, in PD, has an excessively inhibitory effect on the thalamus. Therefore the thalamus increases in it’s excitation of the motor cortex, hypothetically improving symptoms.
What are the side effects of pallidotomies?
- Bilateral pallidotomies cause speech deficits, and even used to cause mutism.
- Unilateral can be effective at reducing PD, but can impair language learning if performed on the dominant hemisphere, or visuospatial processing if performed on the non-dominant hemisphere (primarily due to the wrong location being lesioned).
Why can’t dopamine be consumed in diet?
It cannot pass the blood-brain barrier
Which foods can increase the level of dopamine made?
Foods and fruits high in amino acid
Foods high in folic acid
Apples (high in antioxidants)
Watermelon
What is the supposed cause of dyskinesia’s seen after long periods of L-Dopa medication?
Receptors for dopamine in the striatum become more and more sensitive. Any dopamine flips it into excessive movement.
What is the alternative function of dopamine that differentiates slightly depending on whether patients are on or off medication?
Patients are better at learning negative outcomes than they are at learning from positive outcomes, off medication.
When on medication, patients are better at learning following reward compared to punishment.
Clear that L-dopa treatment modulates some form of efficiency of the direct and indirect pathways, which are differentially influenced by reward and punishment.
What does increased and decreased activity in basal ganglia circuit loops lead to?
Increased leads to reward
Decreased leads to aversion (negative approach behaviour)
