7 - the basal ganglia

Question 1

what makes up the striatum?

Answer 1

putamen and caudate nucleus

Question 2

what does the lentiform nucleus consist of?

Answer 2

putamen and globus pallidus

Question 3

what separates the lentiform nucleus from the caudate and thalamus?

Answer 3

internal capsule

Question 4

what can basal ganglia dysfunction cause?

Answer 4

movement disorders

• hypokinetic — too little movement eg. Parkinson’s
• hyperkinetic — too much movement, often abnormal involuntary movements

Question 5

what is the input region of the basal ganglia?

Answer 5

striatum

Question 6

what are the output regions of the basal ganglia?

Answer 6

globus pallidus internal and SNr

Question 7

what is the main inhibitory neurotransmitter?

Answer 7

GABA

Question 8

what are the main neurones in the striatum? describe them

Answer 8

medium spiny neurones — have a number of dendritic spines — vastly increases SA of neurones (lots of spines) allowing very fine tuning of signal in those neurones

= projection neurones

Question 9

what neurotransmitter do medium spiny neurones use?

Answer 9

GABA +/- neuropeptides

Question 10

what are the other type of neurone in the striatum?

Answer 10

interneurons
- modulate transmission withi the neural networks of the striatum
- there are GABAergic interneurons and cholinergic (large aspiny neurones)

Question 11

what input does the striatum have?

Answer 11

1. glutamatergic cortciostriatal pathway = input from all regions of cerebral cortex
2. dopaminergic nigrostriatal pathway = from SNc

Question 12

what pathway is damaged in parkinson’s?

Answer 12

nigrostriatal pathway

Question 13

the interaction between what controls the level of activity within the striatum?

Answer 13

dopamine and glutamate

Question 14

what kind of input is striatal input?

Answer 14

excitatory

Question 15

what does the input from the whole cerebral cortex excite?

Answer 15

medium spiny neurons

Question 16

DA regulates the activity of what?

Answer 16

medium spiny neuroens

Question 17

where is DA produced?

Answer 17

SNc

Question 18

what type of output is the output from medium spiny neurones?

Answer 18

inhibitory

Question 19

glutamate from corticostrial neurone acts on what receptors?

Answer 19

ionotropic AMPAR and NMDAR receptors and metatrobic receptors mGluR on tip of spine of MSN

Question 20

what interact to modulate synaptic strength?

Answer 20

dopamine and glutamate

Question 21

what is key to long term potentiation?

Answer 21

dopamine — without dopamine the long-term enhancement of synaptic strength doesnt happen

dopamine alters level of activity in the neuron

Question 22

what neuropeptide is in the direct pathway?

Answer 22

dynorphin substance P

Question 23

what neuropeptide is used in the indirect pathway?

Answer 23

enkephalin

Question 24

what receptors are used in the 2 pathways?

Answer 24

direct = D1
indirect = D2

Question 25

the output of the basal ganglia is overall what?

Answer 25

inhibitory

Question 26

how does D1 receptor enhance neuronal activity?

Answer 26

G protein coupled with GaS — activates adenylyl cyclase to convert ATP —> cAMP which allows the phosphorylation/activation of intracellular substances

Question 27

how does the D2 receptor decrease neuronal activity?

Answer 27

coupled with Gi/o which inhibits adenylyl cyclase

Question 28

direct vs indirect pathway functions

Answer 28

D1 = facilitation of desired movements D2 = suppression of unwanted movements

Question 29

how is dopamine released in resting conditions?

Answer 29

tonic dopamine release — low synaptic levels and extra synaptic levels — preferential D2R activation indirect pathway neuroens higher excitability at rest — action inhibiton “no-go” long term depression indirect pathway overactive at rest

Question 30

how is dopamine released in active movement?

Answer 30

phasic dopamine release — preferential D1R activation — motor initiation, enhances motor learning via long-term potentiation

Question 31

what is the hyper direct pathway?

Answer 31

- from cortex to STN - additional role in inhibitory control (enhance fine tuning of inhibition)

Question 32

describe the dorso lateral to ventromedial in terms of function in the basal ganglia?

Answer 32

dorslolateal = more motor ventromedial = more limbic

Question 33

there are parallel loops in the basal ganglia subserving different functions such as what?

Answer 33

eye movements, limbic

Question 34

what happens in parkinson’s to the 2 pathways?

Answer 34

- degeneration of SNc — loss of dopamine - reduced D1 activation — reduced excitation - reduced D2 activation — less (-) stimulation

Question 35

there is the relative overactivity of what in parkinson’s? what is the result?

Answer 35

indirect pathway — reduced voluntary movement (bradykinesia), rigidity

Question 36

why is there impaired motor learning in parkinson’s?

Answer 36

loss of long term potentiation as dopamine and glutamate don’t interact to facilitate motor learning

Question 37

what is the subthalamus like in parkinson’s?

Answer 37

over active — lesion of STN alleviates experimental parkinsonism

Question 38

what are cognitive disturbances in PD linked to?

Answer 38

- linked to changes in DA handling in basal ganglia loops

Question 39

what is later dementia in PD related to?

Answer 39

cortical spread of Lewy body pathology

Question 40

what impulsive behaviour are there in PD?

Answer 40

pathological gambling, hyper sexuality, compulsive eating

Question 41

what is impulsive behaviour in PD linked to?

Answer 41

more severe dopaminergic deficit in ventral (limbic) striatal area

Question 42

what is depression and anxiety in PD linked to?

Answer 42

monoamine cell loss in brainstem

Question 43

what may improve depression in PD?

Answer 43

dopamine agonists

Question 44

what are 2 choreiform disorders?

Answer 44

Huntingtons disease and levodopa-induced dyskinesia

Question 45

what is chorea?

Answer 45

- rapid, multi focal irregular movements - flitting between various muscle groups and body parts - motor impersistence

Question 46

pathophysiology of chorea

Answer 46

- imbalance between direct and indirect pathways - relative overactivity of direct pathway — excessive movement - underactivity of indirect pathway — no suppression of unwanted movements

Question 47

pathophysiology of Huntingtons disease

Answer 47

- selective loss of D2 receptor-bearing indirect pathway neurones —> involuntary movements - later loss of direct pathway neurons —> hypokinetic movement disorders

Question 48

in Huntington’s disease there is loss of neuroens in what layers of the cortex?

Answer 48

layers V and VI

Question 49

striatal pathology in Huntington’s disease

Answer 49

degeneration in caudate and indirect pathway D2 receptor-bearing medium spiny neurones

Question 50

what neuropsychiatric disturbances are there in Huntington’s disease?

Answer 50

- anxiety, depression - impulsivity, apathy

Question 51

what is a potential treatment to Huntington’s disease?

Answer 51

cell transplantation — replace MSNs

Question 52

what is enkephalin like in huntington’s disease?

Answer 52

rapidly reduced

Question 53

describe tourette syndrome

Answer 53

- tic disorder - usually onset age <20 - rapid, repetitive, stereotyped movements or vocalisations - frequent comorbid neuropsychiatric illness

Question 54

pathophysiology of tourette syndrome

Answer 54

- loss of cholinergic and GABAergic striatal interneurones — reduced basal ganglia inhibition - increased striatal dopamine D2 receptor binding in patients with TS

Question 55

how a tic disorders treated?

Answer 55

- anti dopaminergic therapy - alpha receptor agonists - clonidine, helpful for ADHD symptoms too - deep brain stimulation (GPm/thalamic DBS may help in some cases)

Question 56

Answer 56

Question 57

Answer 57

Question 58

what is hemiballismus?

Answer 58

Hemiballismus is a hyperkinetic involuntary movement disorder characterized by intermittent, sudden, violent, involuntary, flinging, or ballistic high amplitude movements involving the ipsilateral arm and leg caused by dysfunction in the central nervous system of the contralateral side thrashing movement contralaterally. caused by a subthalamic stroke