Synapse Stabilisation and Maturation

Question 1

What is polyinnervation?

Answer 1

Motor neurons initially innervate multiple muscle fibres, and each fibre receives multiple inputs

Question 2

What is monoinnervation?

Answer 2

single motor neuron innervating a single fibre- this happens over time as synapses retreat in development to a mature animal

Question 3

Why does polyinnervation lead to discoordination?

Answer 3

Multiple motor neurons innervating a single muscle fiber may lead to conflicting signals, causing uncoordinated contraction. - reduced by competition over timethrough synapse elimination leading to monoinnervation

Question 4

How is a TTX Cuff (Sodium Channel blocker) used to block polyinnervation -monoinnervation transition?

Answer 4

• More poly-neuronally innervated muscle fibres
• Reduction in synapse loss
• Shows synapse activity is essential for synapse elimination

Question 5

What is the primary determinant of survival?

Answer 5

• The coordinated electrical activity between the pre (motor neuron) and post (muscle fibre) synaptic cells

Question 6

How can we see that electrical activity is the primary determinant of survival?

Answer 6

• Disconnect muscle contraction (no electrical activity inside)
• Replace with externally firing electrodes which fire at random
• This ACCELERATES SYNAPSE ELIMINATION because it shows non-efficiency and a lack of coordination

Question 7

What converts coordinated electrical activity into survival of the synapse?

Answer 7

• So, MMP controls the processing of pro BDNF (neurotrophin) to mature BDNF
• Coordinated electrical activity leads to high MMP expression
• More MMP = More mature BDNF = More BDNF binding to its receptors (Trkb) = ‘reward signal’ into presynaptic cell favouring competition

If the pro-BDNF is not processed due to a lack of MMPs (Uncoordinated signalling) it will bind to p75 which leads to synaptic elimination

Question 8

What is the evidence for the process of converting electrical activity into the survival of a synapse?

Answer 8

• Blockage of Trkb accelerates synapse elimination in vivo
• Inhibition of MMP prevents synapse strengthening
• Loss of p75 prevents synapse elimination
• Addition of proBDNF accelerates synapse elimination

Question 9

What are occular dominance columns?

Answer 9

• A way to visually map the info coming from the retina to the cortex
• Visual pathway sends projections ot the LGN and spatial representation is preserved so left and right eye information get layered into different columns
• Can be seen by injecting radioactive amino acid into one eye (gets incorporated into proteins) and not the other, can see stripes

Question 10

What is the difference in the occular dominance columns between when the eye has and hasn’t opened yet?

Answer 10

Ferret 3 weeks after eye open = Occular dominance columns
Before eye opens = Left and right eye domains not separated

Do retinal ganglion neurons fire due to light stimulation and therefore cause formation of ocular dominance columns?

Question 11

How do ocular dominance columns link to synaptic competition?

Answer 11

All cells in the visual cortex layers respond to light, inputs coming from the LGN comes into layer 4
- In binocular vision you see proper separating and labelling
- If you prevent one eye from opening (monocular deprivation) the open eye takes full representation in the brain, its layer 4 neurons spreading over layers 2 and 3
- Synaptic elimination of the ‘deprived’ eyes neurons due to overwhelming competition of open eye
- Can see ocular dominance in the columns

Question 12

How does long term potentiation occur?

Answer 12

Repeated high frequency stimulation of the pre synaptic cell results in long-lasting increased post-synaptic response (EPSP)

Question 13

How does Long term depression occur?

Answer 13

Low frequency stimulation of pre synaptic cell resulting in long term decreased post synaptic response leading to subsequent action potentials

Question 14

What is the effect of glutamate on the hippocampal neurons?

Answer 14

Controls whether the response is either potentiation or depression

Question 15

What does the release of glutamate do?

Answer 15

• Glutamate released from pre-synaptic glutamate into the synapse, picked up by NMDA receptor and AMPA receptor
• If depolarising levels of Na+ flow through AMPA in response to glutamate release, this unblocks NMDA channels releasing a Ca2+ signal into the cell
• So, NMDA is activated in response to presynaptic glutamate release and postsynaptic action potentials (called a coincidence detector)
  The Ca2+ signal has a number of effects that leads to synaptic potentiation

Question 16

What are the effects Ca2+ has on synaptic potentiation

Answer 16

1. Post synaptic changes in the number of AMPA receptors and responsiveness which leads to an increase in long term potentiation
2. Size of dendrite membrane increases (increase in synaptic size)
3. Pre synaptic changes in neurotransmitter release due to retrograde signals, retrograde signals increase neurotransmitter release

Question 17

What happens if you block NMDA in terms of monocular deprivation?

Answer 17

Stops synaptic plasticity of ocular dominance

Question 18

Give an example of a monosynaptic spinal reflex circuit

Answer 18

Motor neurons innervating the triceps and pectoral muscles develop monosynaptic connections directly with proprioceptive neuron

Question 19

Give an example of a polysynaptic spinal reflex circuit

Answer 19

Between the Motor neurons and the cutaneous maximus, there is an interneuron , meaning there are several synapses in the loop

Question 20

What are the differences in spinal reflex circuits controlled by?

Answer 20

-The target muscle
- GDNF secreted from target muscles and received by motor neurons.
- GDNF turn on transcription factors which affect the whole way which the circuit is made