Case 7 - Basal Ganglia Lecture

Question 1

what is meant by hypokinetic

Answer 1

too little movement

Question 2

what is meant by hyperkinetic

Answer 2

too much movement
often abnormal involuntary movements

Question 3

what can both of these be caused by

Answer 3

basal ganglia dysfunction

Question 4

what is the input nucleus

Answer 4

the striatum made up of the caudate and putamen

Question 5

what is the D1 pathway

Answer 5

this pathway projects directly to the globus pallius media - contains GABA which is the main inhibitory neurotransmitter and that projects directly to the GPm D1 dopamine receptors

Question 6

what are the output regions of the basal ganglia

Answer 6

the globus pallidus media along with the substantia nigra pars reticulate

Question 7

where does the indirect pathway project

Answer 7

to the GPl and then to the output region, the medial globus pallidus via another GABA transmission pathway to the sub thalamic nucleus which then projects back using glutamate to the medial globes pallidus

Question 8

features of the striatum

Answer 8

comprises the caudate and putamen
input region of the basal ganglia

Question 9

what are medial spiny neurones

Answer 9

dendritic spines

Question 10

what do medium spiny neurones do

Answer 10

vastly increase surface area and are 96% of striata neurones

Question 11

medium spiny neurones are ……..ergic

Answer 11

GABAergic ± neuropeptides

Question 12

what are internueones

Answer 12

don’t project outside of the striatum

Question 13

features of interneurones

Answer 13

GABAergic
Cholinergic (large aspiny neurones)

Question 14

where does striatal input come form

Answer 14

corticostriatal pathway and nigrostriatal pathway

Question 15

features of the corticostriatal pathway

Answer 15

glutamaterguc
inout from the whole cerebral cortex

Question 16

features of the nigrostrital pathway

Answer 16

dopaminergic
from substantia nigra pars compatacta
projects to the striatum
interaction of dopamine and glutamate which controls the level of activity in the striatum
dopamine regulates and fine tunes the output of the basal ganglia

Question 17

what do dopamine and glutamate interact to do

Answer 17

modulate synaptic strength

Question 18

what are the neuropeptides in the direct pathway

Answer 18

dynorphin and substance P

Question 19

what are the neuropeptides in the indirect pathway

Answer 19

enkephalin

Question 20

what is the dynorphin precursor

Answer 20

PPE-B

Question 21

what is the enkephalin precursor

Answer 21

PPE-A

Question 22

where does the D1 receptor mainly act

Answer 22

on g-alpha-s subunits - excitatory and activates adenyl cyclase which leads to cAMP formation

Question 23

where does the D2 receptor mainly act

Answer 23

on inhibitory G protein subunits which inhibits adenylyl cyclase and leads to less activation of cAMP

Question 24

diagram of basal ganglia organisation

Answer 24

Question 25

what does the D2 pathway involve

Answer 25

The suppression of unwanted movements

Question 26

what does the D1 pathway involve

Answer 26

the facilitation of wanted movements

Question 27

what is the action of dopamine in resting conditions

Answer 27

Question 28

what are the actions of dopamine in active movement

Answer 28

Question 29

What is the hyper direct pathway

Answer 29

additional role in inhibitory control parallel loops subserving different functions dorsolateral to ventromedial gradient in terms of function

Question 30

where is the hyper direct pathway from

Answer 30

the cortex to the STN

Question 31

what happens if there is a loss of dopamine in the direct pathway

Answer 31

reduced excitation

Question 32

what happens if there is a loss of dopamine in the indirect pathway

Answer 32

reduced inhibition

Question 33

diagram demonstrating the basal ganglia in Parkinson

Answer 33

Question 34

is there an increase or decrease of enkephalin in parkinsons

Answer 34

increase in enkephalin

Question 35

is there an increase or decrease of dynorphin in parkinsons

Answer 35

decreased production of dynrophin

Question 36

what is the net result

Answer 36

is there is less inhibition of the output regions of the basal ganglia via the direct pathway and there is too much excitation via the indirect pathway

Question 37

what does this therefore lead to

Answer 37

the output from the basal ganglia is increased - increased inhibition of the brainstem and spinal cord and increased inhibition of the motor part of the thalamus this leads to reduced excitatory output from the thalamus and reduced excitation of the cortex which leads to less movement

Question 38

what is the pathophysiology of Parkinsonism

Answer 38

relative overactivity of the indirect pathway suppression of movement which leads to bradykinesia and rigidity impaired motor learning - loss of LTP subthalamic overactivity - lesions of STN alleviates experimental Parkinsonism and effects of lesion surgery?

Question 39

what are the cognitive disturbances linked too in PD

Answer 39

changes in dopamine handling in basal ganglia loops later dementia related to cortical Lewy body pathology

Question 40

impulsive behaviour in PD:n

Answer 40

pathological gambling, hypersexuality and compulsive eating linked to more severe dopaminergic deficit in ventral (limbic) striata areas

Question 41

depression and anxiety in PD

Answer 41

related to monoamine cell loss in the brainstem dopamine agonists may improve depression in PD

Question 42

what are hyperkinetic choreiform disorders

Answer 42

huntinngtons disease Levodopa induced dyskinesia dystonia tic disorders

Question 43

what is Chorea

Answer 43

rapid, multifocal irregular movements flitting between various muscle groups and body parts motor impersistence

Question 44

what is the pathophysiology of chorea

Answer 44

imbalance between direct and indirect pathways relative overactivity of direct pathway - excessive movement under activity of indirect pathway - no suppression of unwanted movement

Question 45

what is Huntington's disease

Answer 45

expanded CAG repeats in Huntington Gene (chromosome 4p16.3) complete penetrance with over 40 repeats anticipation, greater expansion with male transmission

Question 46

what is the pathophysiology of Huntingtons

Answer 46

selective loss of D2 receptor bearing indirect pathway neurones --> involuntary movements later loss of direct pathway neurones --> hypokenetic movement disorder

Question 47

what is the cortical pathology in HD

Answer 47

loss of neurones in layers V and VI

Question 48

what is the striatal pathology

Answer 48

degeneration in caudate and indirect pathway D2 receptor bearing MSNs

Question 49

diagram for the basal ganglia in HD

Answer 49

Question 50

what is Tourette syndrome

Answer 50

tic disorder, usually onset age of less than 20 rapid, repetitive stereotyped movements or vocalisations frequent comorbin neuropsychiatric illness

Question 51

what is the pathophysiology of touettes

Answer 51

loss of cholinergic and GABAergic striata interneurones increased striata dopamine D2 receptor binding in patients with TS compared to controls

Question 52

what are the therapies used in tic disorders

Answer 52

antidopaminergic therapy - tetrabenzine antipsychotic agents - haloperidol, sulphide (block D2 receptor) alpha receptor agonists - clonidine