Basal ganglia and movement disorders

Question 1

What is the major output of the basal ganglia?

Answer 1

GPi + SNPR to thalamus

Question 2

What is the major input of the basal ganglia?

Answer 2

Cortex to striatum

Question 3

Which nucleus of the basal ganglia releases dopamine?

Answer 3

Substantia nigra

Question 4

On which basal ganglia nucleus does dopamine act?

Answer 4

Striatum

Question 5

What is the main type of neuron in the striatum?

Answer 5

Medium spiny neurons

Question 6

Which glutamate receptor is involved in long-lasting synaptic plasticity?

Answer 6

NMDA

Question 7

Activated AMPA receptors allow the influx of which ions?

Answer 7

Na+

Question 8

Activated NMDA receptors allow the influx of which ions?

Answer 8

Na+ and Ca+

Question 9

Before they open, what are NMDA receptors initially blocked by?

Answer 9

Mg2+ ions

Question 10

Do medium spiny neurons have high or low excitability?

Answer 10

Low

Question 11

What are the 2 glutamate receptors?

Answer 11

AMPA
NMDA

Question 12

What are the 2 GABA receptors?

Answer 12

GABA(A)
GABA(B)

Question 13

Is AMPA ionotropic or metabotropic?

Answer 13

Ionotropic

Question 14

Is NMDA ionotropic or metabotropic?

Answer 14

Ionotropic

Question 15

Is GABA(A) ionotropic or metabotropic?

Answer 15

Ionotropic

Question 16

Is GABA(B) ionotropic or metabotropic?

Answer 16

Metabotropic

Question 17

Activated GABA(A) receptors allow the influx of which ions?

Answer 17

Chloride

Question 18

Activated GABA(B) receptors allow the efflux of which ions?

Answer 18

K+

Question 19

Dopamine is synthesised from what?

Answer 19

Tyrosine

Question 20

Where in the neuron is dopamine synthesised?

Answer 20

Presynaptic terminals

Question 21

Dopamine is taken up into the presynaptic terminals for recycling via what?

Answer 21

Dopamine transporter (DAT)

Question 22

Dopamine is repackaged into vesicles to be recycled via what?

Answer 22

Vesicular monoamine transporter (VMAT)

Question 23

Describe the chain of events when dopamine binds to D1 receptors and how this facilitates movement.

Answer 23

D1 receptors activate adenylyl cyclase, which converts ATP into cyclic AMP (cAMP)

cAMP activates protein kinase A, which increases neuron excitability and enhances signalling

Question 24

Where does dopamine have an effect in the indirect pathway?

Answer 24

It reduces inhibition of GPe by the striatum

Question 25

The main motor symptoms of Parkinson's disease can be remembered by TRAP - what does this stand for?

Answer 25

Tremor Rigidity Akinesia Postural instability

Question 26

Which 2 types of rigidity are seen in Parkinson's disease?

Answer 26

Lead-pipe rigidity Cogwheel rigidity

Question 27

What happens to a patients handwriting with Parkinson's disease?

Answer 27

Micrographia

Question 28

What percentage of cases of Parkinson's disease are genetic?

Answer 28

10%

Question 29

What are the 2 autosomal dominant genes that cause Parkinson's disease?

Answer 29

Alpha-synuclein Dardarin

Question 30

What are the 4 autosomal recessive genes that cause Parkinson's disease?

Answer 30

Parkin PINK1 DJ1 ATP13A2

Question 31

Dopamine travels from the substantia nigra pars compacta to the striatum via which pathway?

Answer 31

Nigrostriatal pathway

Question 32

Why is the substantia nigra black?

Answer 32

Due to the accumulation of neuromelanin - a by-product of dopamine synthesis

Question 33

Which protein forms aggregates in Parkinson's disease? What does this protein aggregation lead to the formation of?

Answer 33

Alpha-synuclein Aggregation of alpha-synuclein leads to the formation of Lewy Bodies

Question 34

What is the main protein in Lewy Bodies?

Answer 34

Alpha-synuclein

Question 35

In which 2 areas does Lewy body pathology usually begin in Parkinson's disease?

Answer 35

Medulla and olfactory bulbs

Question 36

In Parkinson's disease, what is Braak staging?

Answer 36

The progression of Lewy body pathology

Question 37

How can Lewy bodies affect cell membranes and how can this lead to cell death?

Answer 37

Lewy bodies can form pore-forming complexes in the cell membrane, leading to an influx of calcium, which in excess would cause cell death

Question 38

An abnormality in which process may be responsible for the aggregation of alpha-synuclein?

Answer 38

Abnormal phosphorylation

Question 39

What are the 3 main mechanisms of cell death in Parkinson's disease?

Answer 39

Protein aggregation Abnormal ubiquitin-proteasome system Mitochondrial dysfunction

Question 40

Huntington's disease is caused by an abnormality in which gene / protein?

Answer 40

Huntingtin gene

Question 41

What is the genetic mutation responsible for Huntington's disease?

Answer 41

CAG repeats

Question 42

Does Huntington's disease involve inclusions or plaques?

Answer 42

Inclusions

Question 43

In Huntington's, there is a selective loss of medium spiny neurons in the striatum associated with which pathway?

Answer 43

Indirect pathway

Question 44

Neurons from which structure of the basal ganglia die in Huntington's disease?

Answer 44

Striatum (specifically medium spiny neurons of the indirect pathway)

Question 45

What is the inheritance pattern of Huntington's disease?

Answer 45

Autosomal dominant