BB2 Revision1 Flashcards
What are the functions of the basal ganlia? [4]
Regulating movement:
* Play a critical role in movement initiation
* Allow switching between motor programs (e.g. stop or start a movement)
* Inhibit antagonistic and unnecessary movements
* Regulate movement force
How can you classify the basal ganglia?
Which nuclei fall into these categories
Dorsal striatum:
- Caudate nucleus
- Putamen
Lentiform nucleus
- Putamen
- Globus pallidus
Label A-F
A: caudate nucleus
B: putamen
C: Globus pallidus external
D: Globus pallidus internux
E: Subthalamic nucleus
F: Substantia nigra (SN)
Where do the following send info to / from?
External segment of globus pallidus [1]
Internal segment of globus palliudus [1]
What is the roles of:
External segment of globus pallidus: relays information between other basal ganglia and internal globus pallidus
Internal segment of globus palliudus: sends output to the thalamus
Blood supply to the basal ganglia:
Label
6
7
8
9
10
11
12
6: Lenticulostriate arteries
7: ACA
8: MCA
9: PCA
10: ICA
11: Basilar artery
12: Vertebral artery
The ACA supplies which part of the basal ganglia? [3]
- Head of caudate
- rostral part of putamen
- globus pallidus
which artery supplies blood to the middle part of the basal ganglia - specifically the internal globus pallidus [1]
Anterior choroidal artery
Label 5, 7, 10, 11, 12 & 13
5: ICA
7: Basilar artery
10: Caudate nucleus
11: Internal capsule
12: Lentiform nucleus (Putamen & Globus pallidus
13: Caudal extremity of caudate
nucleus
Which part of the basal ganglia are the input [1] and output zones [3]?
Input zones:
* Dorsal striatum (caudate nucleus & putamen)
Output zones:
* globus pallidus external
* globus pallidus internal
* substantia nigra, pars reticula (SNr)
Basal ganglia input zones:
Where do the caudate nucleus and putamen have fibres inputing into / orginating from? [3]
- Cerebral cortex - specifically the frontal cortex: primary motor cortex and parietal cortex: primary somatosensory cortex
- substantia nigra pars compacta (from the midbrain)
- Local circuit neurons within the corpus striatum (GABAergic)
Label A-E
What is the name for the type of neurons that recieve the information in the dorsal striatum (caudate nucleus & putamen)
medium spiny neurons
Where do the following output zones of the basal ganglia send information to?
globus pallidus external (GPe) [1]
globus pallidus internal (GPi) [1]
substantia nigra, pars reticula (SNr) [1]
globus pallidus external (GPe): subthalamic nucleus
globus pallidus internal (GPi): ventral anterior (VA) / Ventrolateral (VL) thalamic nuclear complex
substantia nigra, pars reticula (SNr): superior colliculi
Neurons from substantia nigra pars reticula (SNr) synapse onto neurons in the []
Neurons from substantia nigra pars reticula (SNr) synapse onto neurons in the superior colliculus (midbrain)
Describe the concept of double inhibition / disinhibition of the VA / VL complex
The caudate and putamen contain inhibitory GABAergic neurons that project onto
Globus pallidus internal neurones - which are also inhibitory GABAergic neurons
This creates overall excitation
Below is a coronal section of the cerebrum. Which of the following labels corresponds to an intrinsic nuclei of the basal ganglia?
A
B
C
D
Below is a coronal section of the cerebrum. Which of the following labels corresponds to an intrinsic nuclei of the basal ganglia?
A
B
C
D
Describe the direct pathway of the basal ganglia
- Dorsal striatum recieves dopaminergic inputs from the substantia nigra AND glutamatergic input from the association cortexes
- The dorsal striatum releases GABA which projects onto the internal globus pallidus.
- This Increases inhibition on the GPi
4 The GPi then projects less inhbitory GABA onto the motor thalamus - This causes reduced inhibition of motor thalamus (double double inhibition)
- Allows changes in cortical motor program
Describe the indirect pathway of the dorsal ganglia
Excitation of dorsal striatum causes the release of dorsal striatum GABA (inhibitory)
This causes projects onto globus pallidus external segment: causes increased inhibition of GPe
This causes the globus pallidus external segment to release inhibitory GABA onto the subthalamic nucleus: causes reduced inhibition of STN
This causes the subthalamic nucleus to release inhibitory GABA onto the globus pallidus internal segment: which increases the activation of GPi
This causes the globus pallidus internal segment to release inhibitory GABA onto the motor thalamus: which creates increased inhibition of motor thalamus
OVERALL DEACTIVATION OF MOTOR THALAMUS -> decreased motor cortex activation.
NO GO pathway.
Describe how the hyperdirect pathway occurs
Signal from the pre-supplementory motor cortex bypasses the dorsal striatum and causes the release of glutamate (excitatory) onto subthalamic nuclei
This causes activation of subthalamic nuclei, which releases glutamate onto the GPi
Activation of GPi causes release of GABA (inhibitory) to the VA VL thalamus - which stops motor cortex
When at rest or doing a repetitive movement (e.g., talking):
the indirect pathway is []
the direct pathway is []
When at rest or doing a repetitive movement (e.g., talking):
the indirect pathway is active
the direct pathway is inactive
Name the two receptors found in dorsal striatum that activated by neurons from the substantia nigra
substantia nigra has neurons that activate D1 or D2 receptors on dorsal striatum
Describe the effect of the activation of the D1 dopaminergic receptors
The D1 dopaminergic receptor activated:
- Increases cAMP
- Increases the sensitivity of striatal GABA neurons to glutamate (makes the glutatemate MORE EXCITABLE)
- Causes more activation of the direct pathway
End result: INCREASED MOTOR ACTIVITY
Describe the effect of the activation of the D2 dopaminergic receptors
The D2 dopaminergic receptor activated:
- decreases cAMP
- Decreaes the sensitivity of striatal GABA neurons to glutamate (makes the glutatemate LESS EXCITABLE)
- Causes increased inhibition of the sub-thalamic nucleus
- This means get increaed inhibition of the GPi
- This causes less inhibition of the VL / VA
End result: INCREASED MOTOR ACTIVITY
Overall effect of dopamine modulation on basal ganglia:
What is the effect of D1 receptor on direct pathway? [1]
What is the effect of D2 receptor on indirect pathway? [1]
D1 receptors: INCREASES the responsiveness of the direct pathway to cortical inputs
(facilitates the direct pathway)
D2 receptors: DECREASES the responsiveness of the indirect pathway to cortical inputs
(inhibits the indirect pathway)
Is Parkinsons disease a hyperkinetic or hypokinetic disease? [1]
Is Huntingdons disease a hyperkinetic or hypokinetic disease? [1]
Parkinsons: hypokinetic disease
HD: hyperkinetic disease
Explain pathophysiology of Parkinsons disease [2]
-Loss of dopaminergic neurons in the substantia nigra, which project to and innervate the dorsal striatum.
- Less D1 and D2 activation
- The indirect pathway is therefore faciliated and becomes dominant
Name the 3 classic symptoms of Parkinsons disease [3]
bradykinesia, tremor and rigidity.
Name the symptoms of HD [4]
chorea - movement disorder that causes sudden, unintended, and uncontrollable jerky movements of the arms, legs, and facial muscles.
personality changes (e.g. irritability, apathy, depression) and intellectual impairment
dystonia
saccadic eye movements - abruptly change the point of fixation.
Describe the initial pathophysiology of HD
Loss, in the dorsal striatum, of GABAergic medium spiny neurons of the D2 receptors in the indirect pathway
Direct pathway becomes dominant
(Loss of the brake - causes hyperkinetic neurons)
Describe the late stage pathophysiology of HD
Both direct and indirect pathways degenerates: causes rigidity and bradykinesia becomes dominant
Describe what ballismus and Athetosis are [2] and what they’re caused by [2]
Athetosis:
* slow, involuntary regular writhing movements of the fingers, hands, toes and feet (in some cases, arms, legs, neck and tongue
* Lesions to the striatum; often a result of cerebral palsy
Ballismus:
* a type of chorea, usually involving violent, involuntary flinging of one arm and/or one leg (usually one side of the body is affected: Hemiballismus). The movements are wider and more intense than chorea
* Damage to subthalamic nucleus
What is the name for this symptom?
Lesions to which region causes this symptom?
Subthalamic nuclei
Substantia nigra
Pre supplementary motor area
Lentiform nucleus
Dorsal striatum
athetosis
Lesions to which region causes this symptom?
Subthalamic nuclei
Substantia nigra
Pre supplementary motor area
Lentiform nucleus
Dorsal striatum
What is the name for this symptom?
Lesions to which region causes this symptom?
Subthalamic nuclei
Substantia nigra
Pre supplementary motor area
Lentiform nucleus
Dorsal striatum
Ballismus
Subthalamic nuclei
Substantia nigra
Pre supplementary motor area
Lentiform nucleus
Dorsal striatum
Where is dopamine produced in the brain?
Subthalamic nuclei
Substantia nigra
Pre supplementary motor area
Lentiform nucleus
Dorsal striatum
Where is dopamine produced in the brain?
Subthalamic nuclei
Substantia nigra
Pre supplementary motor area
Lentiform nucleus
Dorsal striatum
alpha-synuclein is endocded by which gene
PARK7
SNCA
LRRK2
PRKN
alpha-synuclein is endocded by which gene
PARK7
SNCA
LRRK2
PRKN
Which mitochondrial metabolite is toxic to dopaminergic pathways? [1]
MPP+
MPP+ is disruptive to
complex I of the mitochondrial respiratory chain
complex II of the mitochondrial respiratory chain
complex III of the mitochondrial respiratory chain
complex IV of the mitochondrial respiratory chain
MPP+ is disruptive to
complex I of the mitochondrial respiratory chain
complex II of the mitochondrial respiratory chain
complex III of the mitochondrial respiratory chain
complex IV of the mitochondrial respiratory chain
Describe in detail the classic triad of motor symptoms of Parkinson’s [3]
Bradykinesia
* poverty of movement also seen, sometimes referred to as hypokinesia
* short, shuffling steps with reduced arm swinging
* difficulty in initiating movement
Tremor
* most marked at rest, 3-5 Hz
* worse when stressed or tired, improves with voluntary movement
* typically ‘pill-rolling’, i.e. in the thumb and index finger
Rigidity
* lead pipe
* cogwheel: due to superimposed tremor
State 5 non-motor features of Parkinson’s disease
- micrographia
- olfactory dysfunction
- depression
- psychotic symptoms
- cognitive dysfunction
- dementia (late phase)
- sleep disturbance
- bladder and bowel dysfunction
- speech and language changes
Describe the difference in onset of symptoms between motor & non-motor Parkinson’s symptoms
Non-motor features may precede by 12-15 years: likely to involve regions of peripheral and central nervous system
What is the name for the scoring scales used for disability associated with PD? [1]
What is difference between 0% and 100%? [1]
Schwab and England Activities of Daily Living
0%: Vegetative functions
100%: Completely independent - can do chorse without slowness, difficulity or impairment
The genetic link between familial PD is due to a link between which protein? [1] Which gene codes for this protein? [1]
Is PD genetic or environmental? [1]
genetic link with the protein alpha-synuclein coded by SNCA (duplications or triplications cause autosomal dominant familial PD)
disease emergence may be due to interactions environment x genes
Describe the link between mitochondrial toxicity and dopaminergic neurons [1]
What process is diruspted as a result of ^ [1]
The compound MPTP is a toxin which can be transformed into the metabolite MPP+ which is neurotoxic for dopaminergic neurons
Dysfunction of complex I of the mitochondrial respiratory chain
can lead to increased oxidative stress
Which enzyme is critical in the dopamine oxidation process? [1]
What are the products of the dopamine oxidation process? [1]
Monoamine oxidase - break down of dopamine can create free radicals (e.g. H2O2
COME back to dopminergic pathways in teh CNS
Describe the mechanism of creation of dopamine [3]
L-tyrosine –> L-Dopa (Decarboxylated to create..) –> Dopamine
Describe the mechanism of dopamine metabolism [3]
Dopamine –> DOPAC –> Homovanillic acid
Dopamine binds to which two receptors? [2]
What are the subtypes of these receptors? [5]
D1 Family Receptors:
* D1 & D5 subtypes
D2 Family Receptors
* D2, D3 & D4 subtypes
