Deck 29: Regeneration and Repair of Synaptic Connections After Injury

Question 1

After an axon degenerates, which process takes the longest in the repair process?

A) Macrophage recruitment
B) Axotomized neuron dying
C) Schwann cell de-differentiating
D) Endoplasmic reticulum dispersing
E) Myelin sheath degrading

Answer 1

C

Question 2

What might slow the process of "dying back" of a motor neuron resulting from toxic insult?

A) Regular muscle stimulation, such as that which occurs in physical therapy
B) Administration of a specific antitoxin or antidote
C) Pharmacological treatment of an antibody against the toxin or toxicant
D) Placement of electrodes on the skin overlying the muscle to provide constant stimulation
E) Administration of anti-inflammatory drugs

Answer 2

A

Question 3

When an axon is severed, what likely causes the presynaptic cell to withdraw axons?

A) The postsynaptic neuron dying, initiating apoptotic cascades
B) The postsynaptic neuron condensing, and widening the synapse to pull axons away
C) Invading macrophages crowding into the synapse, effectively pushing the presynaptic neuron away
D) The de-differentiation of Schwann cells pulling the postsynaptic neuron away
E) Both the pre- and postsynaptic neurons expressing repulsive cues, such as Slit and its Robo receptor

Answer 3

E

Question 4

When a tissue, such as a muscle membrane, is "super sensitive," this means that it

A) requires more chemical stimulus to excite it than normal.
B) requires less chemical stimulus to excite it than normal.
C) takes longer to excite the tissue than it normally does.
D) takes shorter time to excite the tissue than it normally does.
E) has no relationship to the strength of the stimulus that excites the tissue in question.

Question 5

If a muscle fiber has numerous nerve inputs, what will happen if 10% of those nerve inputs were severed?

A) There will be no response.
B) Adjacent nerves will sprout to replace the 10% that was lost.
C) More nerves amounting to more than 10% will sprout.
D) Fewer nerves amounting to less than 10% will sprout.
E) It depends on the usual activity (workload) of the muscle.

Question 6

Following denervation of a muscle, uniform recordings from a microelectrode along the entire muscle fiber means that

A) ACh receptors were both up-regulated and redistributed themselves along the muscle.
B) ACh receptors increased their affinity for acetylcholine at the end-plate.
C) the end-plate grew, thereby increasing the surface area, which could accommodate more ACh receptors.
D) end-plates became more numerous, covering a greater surface area of the muscle.
E) ACh was released from the presynaptic neuron in higher quantal yield.

Question 7

The binding affinity of ACh for its fetal receptors at the site of innervation vs. that at the end-plate in adult muscle is likely because of the

A) sheer number of receptors that can occupy the respective sites.
B) different subunit composition of between the fetal and adult forms of the receptor.
C) density of the receptors at the site of innervation between the fetal and adult forms of the receptor.
D) size of the presynaptic terminal.
E) differences in surface area between the fetal and adult sites of innervation.

Question 8

What might be a reason for the adult denervated muscle to express fetal ACh receptors?

A) The turnover rate of the adult ε subunit can be decreased.
B) The turnover rate of the α subunit can be decreased.
C) The turnover rate of the δ subunit can be increased.
D) The turnover rate of the α subunit can be increased.
E) When all subunits are expressed, it is easier to eliminate unnecessary ones than it is to add necessary ones.

Question 9

If an experimenter wanted to slow down receptor turnover, one thing they can do is to increase cAMP levels and protein kinase A activity. This means that any subsequent changes in gene expression entails

A) increasing the expression of lysosomal enzymes.
B) decreasing the expression of lysosomal enzymes.
C) increasing the expression of fast-type calcium channels.
D) decreasing the expression of fast-type sodium channels.
E) increasing expression of the ACh receptor subunits.

Question 10

Denervation super sensitivity is highly dependent on

A) ACh receptor number.
B) ACh receptor density.
C) sensitivity to ACh.
D) distance between the site of innervation and that of denervation.
E) strength of the current.

Question 11

If you applied tiny amounts of ACh to muscle, you get excitatory postsynaptic potentials (epsps) on individual muscle fibers. When a muscle is stimulated, however, action potentials are also fired and obscure the epsps. What manipulation can be done to mask the action potentials, thereby revealing the underlying epsps?

A) The application of tiny amounts of ACh
B) The application of tiny amounts of tetrodotoxin
C) The application of tiny amounts of curare
D) The application of substantial amounts of ACh
E) The application of substantial amounts of sodium

Question 12

Calcium influx into the muscle is directly caused by

A) agrin binding to its receptor.
B) sodium influx.
C) increased ACh receptor expression.
D) increased calcium channel expression.
E) potassium leakage.

Question 13

To maintain a constant steady-state high sensitivity level of muscle ACh,

A) muscle must be constantly active.
B) muscle must undergo intermittent naturally occurring denervation.
C) ACh receptors must cluster as discrete sites at the end-plates.
D) ACh receptors must reliably turnover (be regularly synthesized and degraded).
E) Acetylcholinesterase must be inhibited.

Question 14

Although the growth factors, BDNF and NGF, and the ApoE and LIF secreted by Schwann cells and macrophages promote neuronal survival, many other such cytokines can also collect at the site of injury. Such a gathering of these molecules is a normal physiological response to injury but can also inhibit axon re-innervation. This response is called

A) blood clotting.
B) recruitment.
C) inflammation.
D) apoptosis.
E) sprouting.

Question 15

To help regenerate axons, Schwann cells express copious amounts of BDNF and NGF receptors so that the

A) Schwann cells can better survive.
B) Schwann cells can find their place along the axon.
C) Schwann cells can participate in the inflammation process.
D) axon can recruit the Schwann cells to myelinate the former.
E) axon can use the neurotrophins as guidance clues to help them find their postsynaptic target.

Question 16

Evidence points to _______ as a key ingredient in the basal lamina that allows synapses to regenerate following cutting of the nerve and muscle fibers.

A) agrin
B) acetylcholine
C) acetylcholine receptors
D) acetylcholinesterase
E) nerve growth factor

Question 17

Synapse elimination means that the presynaptic axon will first

A) atrophy.
B) withdraw.
C) be phagocytized by nearby astrocytes.
D) be crowded out by existing surviving presynaptic and postsynaptic neurons, forming new synapses.
E) lyse.

Question 18

Suppose an α-motor neuron had five axons, which we will call a, b, c, d, and e synapsing onto a muscle with two fibers ("1" and "2"). Axons a and b innervated muscle fiber 1, while axons c, d, and e innervated muscle fiber 2. Then, axons c and d were severed. What result is likely?

A) Axons c and d would regrow to synapse with muscle fiber 2, restoring their original connections.
B) Axons a and b would withdraw.
C) Axons c and/or d would regrow to synapse with muscle fiber 1, while axon a and/or b withdraws.
D) Axons and/or b would withdraw and synapse with muscle fiber 2.
E) Axons a and b would remain unaffected.

Question 19

If you had a transgenic mouse in which the agrin gene was knocked out, which of the following would your mouse not be able to do?

A) Form neuromuscular synapses
B) Survive past birth
C) Coordinate movements, such as walking
D) Cluster acetylcholine receptors
E) Myelinate axons

Question 20

If you had a transgenic mouse in which the rabsyn gene was knocked out, which of the following would your mouse not be able to do?

A) Form neuromuscular synapses
B) Survive past birth
C) Coordinate movements, such as walking
D) Cluster acetylcholine receptors
E) Myelinate axons

Question 21

In the acetylcholine receptor clustering process, which of the following lasts the longest?

A) MuSK phosphorylation
B) Acetylcholine receptor phosphorylation
C) Acetylcholine receptor movement and clustering
D) Agrin binding to Lrp4
E) Recruitment of ACh receptors aggregates

Question 22

Neuronal regeneration in the adult mammalian CNS does not occur as easily as it does in the immature mammalian CNS because

A) there are more excitatory factors/neurotransmitters in the immature CNS than in the adult.
B) there are more inhibitory factors/neurotransmitters in the immature CNS than in the adult.
C) adult CNS axons have more myelination than that of immature CNS.
D) adult CNS neurons are fully differentiated, compared to that of immature CNS.
E) adult CNS is less permissive overall than is the immature CNS.

Question 23

Because axons in the immature mammalian CNS are not yet myelinated, these neurons are more amenable to regeneration. Which of the following properties of myelin, therefore, would be responsible in preventing such regeneration from occurring?

A) Insulating properties against action potential propagation
B) Physical barrier to axons that are elongating
C) Myelin's basic protein
D) The propagation of inhibitory potentials
E) Lowered neuronal resting membrane potential

Question 24

In a complete spinal cord injury, one of the major impediments to functional recovery is

A) destruction of permissive environments.
B) compromised blood brain barrier.
C) increased expression of inhibitory factors.
D) enhanced gliosis and glial scarring.
E) decreased expression of growth and survival factors.

Question 25

In an incomplete spinal cord injury (as opposed to a complete spinal cord injury), one of the most obvious effects is

A) recovery of motor function.
B) recovery of sensory function.
C) spontaneous recovery of motor function.
D) spontaneous recovery of sensory function.
E) rapid spontaneous recovery of motor function.

Question 26

A patient who has just been through a terrible car accident presents in the emergency room unable to feel or move his legs. The ER surgeon suspects spinal cord damage at the lower lumbar level. To minimize the probability that this patient will be paralyzed for life, the physician should

A) wait and see, just making sure that the patient remains immobile.
B) relieve swelling by administration of anti-inflammatory drugs.
C) administer anti-inflammatory drugs after a week or two has passed.
D) administer antibodies against the proteins that are known to regulate and inhibit neural growth.
E) administer antibodies against the proteins released by glial cells contributing to scar tissue.

Question 27

Why would inhibition of Nogo likely not result in full recovery of locomotor function following spinal cord injury?

A) The complexity of even a simple axotomy is too high that recovery is dependent on a plethora of factors, as well as on the timing of when these factors are active.
B) How Nogo is inhibited, whether by a drug or an antibody, is critical whether full recovery occurs.
C) Nogo is not expressed in amounts high enough that would impact full recovery.
D) Nogo receptors are not expressed in high enough amounts that would impact full recovery.
E) Nogo binds to its receptor with relatively low affinity.

Question 28

In a spinal cord injury, if the concentration and variety of neuroprotective and neurotrophic factors outweighs those of neural inhibitory factors full recovery

A) is imminent.
B) is likely.
C) may still not occur.
D) will not occur.
E) cannot be known for sure.

Question 29

Following spinal cord injury, one of the best ways to help ensure that recovery of function occurs is a(n)

A) aggressive battery of anti-inflammatory drugs.
B) aggressive battery of anti-depressant drugs.
C) reliable and challenging physical therapy regimen.
D) combination of anti-inflammatory drug regimen and physical therapy.
E) combination of anti-inflammatory and antidepressant drug regimen plus physical therapy.

Question 30

What is a plausible reason that, as a treatment, regularly ablating the glial scar will still not result in full recovery of function in a spinal cord injury?

A) Such surgery would deplete neurotrophic and neuroprotective factors.
B) Reactive glial cells will increase scars and gliosis in response to such an intervention.
C) Reactive glial cells will increase their proliferation and therefore, the scars and gliosis in response to such an intervention.
D) The correct timing of when to ablate the scar is unknown.
E) The correct amount to ablate is unknown.

Question 31

One important reason for why olfactory ensheathing glial cells have been investigated as candidates for cell transplant experiments, such as in the spinal cord, is because these cells

A) are easily accessible by researchers.
B) are unique to the olfactory system, where the neurons are constantly replaced throughout life.
C) are easy to manipulate in culture.
D) express high concentrations of neurotrophic factors.
E) are capable of warding off gliosis in the event of injury.

Question 32

If one were to transplant olfactory neurons and their ensheathing glial cells at the lesion site in a spinal cord injury, full recovery would likely still not occur because

A) the spinal cord histology is too dissimilar to that of the olfactory bulb.
B) different intracellular signaling pathways exist in the olfactory bulb as opposed to that of the spinal cord.
C) olfactory neurons are too fragile for such transplant procedures.
D) olfactory neuron re-growth in their new environment lasts for only a short time.
E) ensheathing glial cells die off almost immediately upon being transplanted into their new spinal cord environment, because the latter has too many inhibitory factors associated with large amounts of myelin.

Question 33

For a peripheral nerve bridge to be successful, which of the following must occur?

A) The environment into which the axon is growing must be permissive.
B) The neuron whose axon is extending must be of the same type as those occupying the environment in which they will grow.
C) The growing axon has a limit of only 2 mm.
D) The growing axons must be capable of both anterograde and retrograde transport of proteins.
E) The peripheral nerve bridge must come from the same animal into which a transplant is to be made; i.e., an auto-transplant.

Question 34

Assuming a permissive environment, which intrinsic signaling pathway would most likely not promote successful axon elongation?

A) MAPK
B) PI3K
C) PKA
D) JAK/STAT
E) Apoptotic cascades

Question 35

Intrinsic repair strategies will rely on being able to manipulate the expression profile of proteins involved in both growth-promotion and growth inhibition. One of the most promising ways to target such intrinsic repair strategies so that growth is favored would be to focus on

A) prevention of injury.
B) diet.
C) timing of treatment following an injury-the sooner, the better.
D) epigenetics
E) type of treatment.

Question 36

One of the major differences between an incomplete and a complete spinal cord injury or trans-section is that in the former

A) there is a greater reliance on glial recruitment of cytokines.
B) there is a greater reliance on surviving neuronal axons reorganizing the circuits.
C) there is a greater reliance on physical therapeutic interventions.
D) grafting neural stem cells at the site of injury is more critical.
E) glial scarring represents a major barrier to complete recovery.

Question 37

In a human complete spinal cord injury, _______ would be an appropriate type of cell to graft at the site of the lesion.

A) sciatic neurons
B) spinal cord neurons
C) cerebellar Purkinje neurons
D) olfactory neurons
E) stem cells

Question 38

One of the major impediments of successful full recovery of function following implantation of neural stem cells is that

A) such a strategy works only for physical trauma-based damage (e.g., spinal cord injury), rather than for neurodegenerative diseases (e.g., Alzheimer's).
B) such a strategy works only for neurodegenerative diseases (e.g., Alzheimer's), rather than for physical trauma-based damage (e.g., spinal cord injury).
C) often, neural stem cells fail to adapt to their new host environment.
D) often, the compromised host environment can affect the graft of the stem cells, disabling the latter.
E) neural stem cells must be of the correct phenotype.

Question 39

The basic aim of transplanting neural stem cells into the adult mammalian CNS is to

A) treat a neurodegenerative disease or CNS injury.
B) treat inflammation in the CNS.
C) treat peripheral diseases, such as diabetes, which are known to affect CNS functioning.
D) enhance epigenetic approaches to treat CNS disease or injury.
E) rewrite the genetic programming in CNS neurons as part of the therapeutic regimen against CNS disease or injury.

Question 40

What is the best kind of cells to transplant into the adult mammalian CNS?

A) Adult neurons of the same phenotype as those occupying the area into which the transplant will be made
B) Young neurons (1-2 days postnatal) of the same phenotype as those occupying the area into which the transplant will be made
C) Neurons from the autonomic nervous system
D) Neural stem cells
E) Late embryonic neurons

Question 41

If the axon of a postsynaptic neuron is axotomized, explain what occurs with the presynaptic neuron after it has retracted.

Question 42

What are the pros and cons of severing an axon close to, as opposed to far from, its soma?

Question 43

Propose an explanation for denervation super sensitivity to ACh.

Question 44

Propose an explanation for why if a cut motor nerve is placed on an intact or innervated muscle, no new endplates will form, whereas if the muscle has been denervated or its endplate blocked by -bungarotoxin, new endplate synapses will form.

Question 45

If muscle is kept immobile, such as that which occurs with a broken limb confined inside a cast, explain why axons may not increase sprouting.

Question 46

Briefly describe an experiment to determine whether Ca²⁺ influx is critical for muscle contraction.

Question 47

Apolipoprotein E (ApoE) is a well-known genetic risk factor for a multitude of neurodegenerative diseases, such as Parkinson's and Alzheimer's. Explain, then, how ApoE is not only neuroprotective against oxidative damage, but also promotes neurite extension and adhesion.

Question 48

Compare the clustering of ACh receptors in fetal muscle vs. adult muscle endplate. What is the advantage of the adult form of ACh clustering in the muscle endplate?

Question 49

Propose an explanation for how the basal lamina in the neuromuscular junction promotes synapse regeneration.

Question 50

Explain the sequence of events in which agrin leads to the phosphorylation of ACh receptors.

Question 51

In a microarray mRNA screening experiment, which showed that growth-promoting molecules and their receptors were over-expressed, while growth-inhibiting molecules and their receptors were under-expressed in 9-day-old animal, but the reverse occurred in 12-day-old animals, explain what more conclusive experiment should be done.

Question 52

Explain why in a complete spinal cord injury, there is virtually no hope that the patient will ever functionally recover, whereas in an incomplete spinal cord injury, there is a possibility of some functional recovery.

Question 53

Briefly explain how epigenetic mechanisms can influence peripheral nerve regeneration.

Question 54

Briefly explain why a peripheral nerve bridge would have marginal success in repairing spinal cord injury.

Question 55

Although the Neuronal Relay Strategy can be applied to injury or disease, would it be possible to implement it in a healthy brain to enhance certain functions, such as learning and memory, central blindness or deafness?