neurotrophins

Question 1

which subunit is the active component of NGF?

Answer 1

beta subunit

Question 2

describe what happens to NGF and its receptor when NGF is administered to a growth cone

Answer 2

1. NGF binds to receptor

2. NGF and its receptor is internalised and retrogradely transported from growth cone to cell body

Question 3

what is the high affinity receptor that NGF binds to?

Answer 3

TrkA

Question 4

what is the low affinity receptor that NGF binds to?

Answer 4

p75

Question 5

what is a pro-protein?

Answer 5

a protein that is activated once it is cleaved

Question 6

which Trk receptor does BDNF bind to?

Answer 6

TrkB

Question 7

which animals have no neurotrophins at all?

Answer 7

drosophila

c. elegans

Question 8

list some cytokines that act as survival factors in the nervous system

Answer 8

hepatocyte growth factor
ciliary neurotrophic factor
macrophage stimulating protein

Question 9

why does co-ordinated electrical activity in the pre-synapse and post-synapse lead to survival of the synapse?

Answer 9

the more active the synapse is, the more neurotrophin it takes up via membrane recycling

Question 10

merkel cells

Answer 10

mechanoreceptors sensing touch

are innervated but do not need innervation to differentiate

Question 11

DEFINE: post-synaptic density

Answer 11

accumulation of cytoskeleton and membrane associated proteins at the post-synaptic membrane

Question 12

what is the post-synaptic target of the auditory nerve endbulb?

Answer 12

spherical bushy cell

Question 13

what are the changes occurring when a growth cone turns into a pre-synapse?

Answer 13

1. filopodia retraction - growth cone senses where the target cell is
2. formation of tight junctions between growth cone and post-synaptic neuron
3. addition of membrane and ECM to post-synaptic membrane
4. pre-synaptic vesicles, post-synaptic density, receptors and dense ECM accumulate in the cleft

Question 14

cat visual cortex

Answer 14

• at post natal day 10, more axons are being made + synaptic density increases
  cat is opening its eyes for the first time
  retina receives sensory input —> drives synapse formation

Question 15

what dictates where synapses form?

Answer 15

• site availability –> cell body blocked by astrocytes
• growth cone communicating with target. e.g. if target expresses ACh receptors on membrane, growth cone begins to synthesis ACh + electrical activity occurs
• pre-prepared sites on post-synaptic membrane for growth cone. made by laying down ECM (cadherins and other adhesion molecules)

Question 16

Gephrin protein

Answer 16

binds to glutamate receptor
causes clustering of glutamate receptors in the post synaptic membrane
inject anti-sense RNA –> loss of clustering, glutamate receptors are more diffuse due to no gephrin

Question 17

what is ARIA?

Answer 17

protein released by motor neurons
causes increase in AChR subunit ε mRNA
when synapses mature, ARIA causes replacement of gamma subunit for ε subunit to form mature junctional AChR –> causes synthesis of mature AChR
neuregulin family

Question 18

what do neuregulins do?

Answer 18

pattern developing brain

upregulate NMDA receptors in developing cerebellum

Question 19

what induces receptor clustering?

Answer 19

neural agrin in basal lamina

Question 20

what is the mechanism of agrin?

Answer 20

1. neural agrin in the basal lamina binds to MUSK on muscle cell membrane
2. MUSK associates with rapsyn
   - mediated by complex = RATL and MASC
3. rapsyn brings together ACh receptors, laminin, alpha-dystraglycan, beta-dystraglycan in a plaque

Question 21

describe how synaptic connections are refined by focusing

Answer 21

initially, multiple climbing fibres innervate one purkinje cell
synapse between one climbing fibre and purkinje cell selectively strengthened because of highest activity in climbing fibre + competition
selected climbing fibre translocates from soma to dendrite
other weaker climbing fibres on the soma are eliminated

Question 22

what are some morphological features of synapse specialisation?

Answer 22

• vesicles containing neurotransmitters at pre-synaptic membrane
• narrow cleft - filled with ECM, receptors + tight junctions
• thickened post-synaptic membrane due to post-synaptic density

Question 23

Ig domains

Answer 23

confer stickiness

Question 24

experiment showing the role of agrin

Answer 24

• make neuromuscular junction with chick nerve innervating rat muscle. antibody binding neural agrin stops clustering. antibody binding muscle agrin does not stop clustering.
• remove agrin mRNA from hippocampus using antisense mRNA - synapses decrease

Question 25

what is the hebbian synapse?

Answer 25

coordinated activity of a pre-synaptic terminal and post-synaptic membrane strengthens the synaptic connections between them

Question 26

describe an experiment showing that the neuron’s choice of neurotransmitter depends on the environment

Answer 26

transplant quail sympathetic neuron (adrenergic) into cholinergic site in chick
sympathetic neuron synthesises ACh instead of NA
parasympathetic neruon synthesises NA instead of ACh

Question 27

describe an experiment showing that the target affects the neuron’s choice of neurotransmitter

Answer 27

transplant foot pad tissue (normally cholinergic innervation) into a site that is adrenergic
nerve innervating foot pat synthesises ACh

Question 28

what are silent synapses?

Answer 28

intact, non-functional synapses where a pre-synaptic action potential fails to evoke a post-synaptic signal