Case 7 Flashcards
What is the role of the basal ganglia?
Initiation and execution of movement
Where are the basal ganglia based?
Base of the forebrain
What are the telencephalic elements of the basal ganglia?
Caudate nucleas, putamen, globus palladus (internal and external)
What is the diencephalic element of the basal ganglia?
Subthalamic nucleus
What is the mesencephalic element of the basal ganglia?
Substantia nigra
What is the name given to the caudate and the putamen together?
corpus striatum
what area is target of the cortical input to the basal ganglia?
corpus striatum (caudate and putamen)
What part of the basal ganglia is the output to the thalamus?
globus palladus
What neurones in the corpus striatum receives input from the cortex?
medium spiny neurones
What are the only areas of the cortex that do not project to the corpus striatum?
Primary auditory and primary visual
what part of the corpus striatum do the somatosensory and motor cortices project to?
putamen
what part of the corpus striatum does the prefrontal cortex project to?
caudate
Where do the dopaminergic inputs to the corpus striatum arise from?
substantia nigra pars compacta
What neurotransmitter is used for the cortex to the corpus striatum of the basal ganglia?
glutamate
where on the medium spiny neurones do the dopaminergic cells synapse
the base/shaft of the dendritic spines
What dopamine receptors are part of the D1 receptor family?
1 and 5
What dopamine receptors are part of the D2 receptor family?
2,3,4
What does stimulating a D1 receptor do to the adenyl cyclase activity?
Stimulates adenyl cyclase (increases effect of cortical neurones)
What does stimulating a D2 receptor do to the adenyl cyclase activity?
Inhibits (decreases effect of cortical neurones)
What neurotransmitter do the medium spiny neurones use?
GABA
What is the MAIN output of the basal ganglia? inhibitory or stimulatory
Inhibitory
what are the differences between the two populations of medium spiny neurones?
One population expresses D1 (direct pathway) and another expresses D2 (indirect pathway)
What do the medium spiny neurones of the DIRECT pathway synapse onto?
- globus pallidus internal
- substantia nigra pars reticular
What are the normal impulses of the globus pallidus internal and substantia nigra pars reticular
inhibitory
what happens when the globus pallidus internal and pars reticular are inhibited?
They send less impulses - inhibatory impulses - so in effect they become LESS INHIBITORY
where do the globus pallidus internal and pars reticular project to?
Ventral anterior and ventral lateral thalamus
what happens when the globus pallidus internal and pars reticular send less inhibitory impulses to the thalamus?
the thalamus is able to send more stimulatory impulses to the cortex.
what happens when the globus pallidus internal sends more inhibitory impulses to the thalamus?
the thalamus sends less stimulatory to the cortex
What pathway is the globus palidus external involved in?
Indirect
what pathway is the subthalamic nucleus involved in?
indirect
What does the balance between excitation and inhibition mean of the basal ganglia?
They either facilitate or inhibit the descending pathways
What is the dopaminergic pathway called that connects the pars compacta and the basal ganglia?
Nigrostriatal pathway
What is the role of the cerebellum?
acts as a comparator of movement
If there is a mismatch between what the muscles should be doing and what the signals from the muscles show them actually doing, then it sends signals to correct the movement, so that it is performed in a smooth, coordinated fashion
What are the gyri called in the cortex of the cerebellum?
folia
Functionally, what are the three areas of the cerebellum?
- spinocerebellum
- cerebrocerebellum
- vestibulocerebellum
What is the predominant output pathway of the cerebellum?
superior peduncle.
What does the superior peduncle go between?
Midbrain and posterior lobe of cerebellum
What information does the middle cerebellar peduncle carry?
Information from the motor cortex about the desired body parts
What does the middle peduncle go between?
the pontine nuclei and posterior lobe of cerebellum
What information does the inferior cerebellum carry?
Sensory information about the actual position of body parts
What does the inferior peduncle go between?
Medulla and anterior lobe of the cerebellum.
What is cerebellar ataxia?
Jerky and imprecise movements due to pathology in the cerebellum.
What family of hormones does dopamine come from?
catecholamine
what is dopamine involved in?
Motivation, reward and reinforcement
What happens to L-DOPA to form dopamine?
carboxyl group removed
What catalyses the formation of dopamine from L-DOPA
DOPA decarboxylase
What is dopamine derived from?
tyrosine
What catalyses the formation of L-DOPA from tyrosine?
tyrosine hydroxylase
What terminates the action of dopamine?
sodium ion-dependent dopamine transporter
How does dopamine work?
Activating G-protein coupled receptors
what are d1 receptors coupled to?
Gsalpha, which ↑intracellular [cAMP] by activating adenylyl cyclase
What are d2 receptors coupled to
Gialpha, which ↓ [cAMP] by inhibiting adenylyl cyclase
What are the 4 different pathways that use dopamine?
- nigostriatal pathway
- mesolimbic
- mesocortical
- tuberoinfundibular
Where does the mesolimbic pathway go between?
Ventral tegmental area in the midbrain to limbic regions
where does the mesocortical pathway go between?
Ventral tegmental area in the midbrain to limbic regions
What is the action of dopamine in the tuberoinfundibular pathway?
inhibit prolactin release from pituitary
What are the characteristics of parkinsons disease?
(1) resting tremor
(2) increased muscle tone- stiffness
(3) Slowness of voluntary movement-bradykinesia
(4) Difficulty maintaining balance
How many people does PD affect over 40?
1 in 250
How many people does PD affect over 65?
1 in 100
How many people does PD affect over 80?
1 in 10
What toxic substance can people be exposed to that causes PD
MPTP
What does MPTP do?
crosses the BBB and converted to a toxic metabolite., then destroys the nigral dopaminergic neurones
Exposure to what substances can cause PD
MPTP and manganese oxide
What is the most common genetic cause of PD?
Leucine rich repeat kinase 2
What does leucine rich repeat kinase 2 encode
dardarin
What gene is the most common cause of recessive early onset PD?
parkin
What 4 genese cause recessive early onset parkinsons?
- parkin
- DJ1
- Pink1
- ATP13A2
What is an oxidation product of dopamine that gives SNpc its characteristic colour
neuromelanin
What is neuromelanin?
an oxidation product of dopamine that gives SNpc its characteristic colour
what is the overall pathophysiology of PD?
death of dopamine-generating cells in the substantia nigra
What compensatory measures may be taken in the brain in PD?
- boost level of activity of pigment cells
- increase sensitivity of cells of the striatum
What neurotransmitter is also adversely affected in PD?
Acetylcholine
What is micrographia?
abnormally small, cramped handwriting, or the progression to continually smaller handwriting
What is the most popular test for parkinsons?
rapid repetitive finger tapping of the index finger onto the thumb for about 20s on each hand
How is Bradykinesia in the leg tested in PD?
fast foot tapping
What is catelepsy?
transient fixed posturing of a hand after completing a motor task
What is the diagnosis of PD based on?
- careful history taking
- Good response to L-DOPA
What is paresis?
Weakness of voluntary movement
where is the basal ganglia in the brain?
Lateral to and surrounding the thalamus
What is the purpose of the spines present on medium spiny neurons?
It allows them to receive inputs from a variety of cortical, thalamic and brainstem structures
