Deck 5: Wiring of the Visual System

Question 1

Roger Sperry surgically rotated an amphibian's eye, severed the optic nerve, and allowed the retinal ganglion cells to re-grow into the brain. Based on the animal's movements in the opposite direction from its prey, the RGC axons made connections to the same part of the brain as before. If normal vision had been restored, what would he have concluded?

Answer 1

That result would provide support for the 'functional selection hypothesis,' in which initially exuberant connections are selected through their functions to stabilize the final connection pattern.

Question 2

When Sperry and colleagues ablated the dorsal RGCs, the remaining ventral RGCs projected to the dorsal tectum. Conversely, when they ablated the ventral RGCs, the remaining dorsal RGCs projected to the ventral tectum.
A. What are some plausible models for dorsoventral patterning suggested by these results?
B. Ephrins and Ephs are distributed in dorsoventral gradients in both structures. EphB1 is expressed in the tectum, in a low-dorsal to high-ventral gradient. Ephrin-B1 and ephrin-B2 are expressed in the retina in a high-dorsal to low-ventral gradient. What do these expression patterns suggest about the mechanism used for dorsoventral patterning of RGCs projecting to the tectum?
C. A stripe assay was prepared in which stripes of artificially clustered EphB1 receptor extracellular domain were prepared on a polylysine coated coverslip. Based on your model, how would you expect the axons of dorsal retinal explants to behave in this assay?

Answer 2

Perhaps dorsal RGCs are attracted to the ventral tectum and/or repulsed by the dorsal tectum. Conversely, perhaps ventral RGCs are attracted to the dorsal tectum and/or repulsed by the ventral tectum.
B. According to these data, the RGCs expressing a high level of ephrin-B project to the part of the tectum with a low level of EphB. This suggests a mechanism of reverse signaling, with activation of ephrin-B by EphB mediating attraction of dorsal axons to the ventral tectum.
C. The dorsal axons should preferentially grow on the stripes containing EphB1.

Question 3

In chick, ephrin-A2 is found in an increasing gradient from anterior to posterior tectum. Researchers virally misexpressed ephrin-A2 in patches throughout the tectum and then visualized the temporal RGC axons that expressed high levels of its receptor EphA3. What result would demonstrate the sufficiency of ephrin-A2 for repulsion?

Answer 3

If ephrin-A2 is sufficient to repulse RGC axons expressing EphA3, then the temporal axons should target the anterior tectum but avoid the patches of virally misexpressed ligand.

Question 4

Arrange the following events into their chronological order during monkey development. A. Consolidation of ocular dominance columns in layer 4 of primary visual cortex
B) Eye-specific segregation of RGC axons at the LGN
C) Formation of ocular dominance columns in layer 4 of primary visual cortex
D) Arrival of RGC axons at the LGN
E) Onset of vision

Question 5

Based on the competition model, what would be the expected result if the temporal axons could be ablated early in development (before they had grown into the tectum/SC)?

Question 6

Monocular deprivation of cats during the critical period (about four through twelve weeks after birth) results in profound and irreversible effects on:
(a) retinal responses.
(b) LGN neuron responses.
(c) the initial formation of ocular dominance columns in layer 4 of primary visual cortex.
(d) the consolidation of ocular dominance columns in layer 4 of primary visual cortex.
(e) All of the above

Question 7

Netrin was first discovered in a biochemical assay for the attraction of vertebral commissural axons to floor plate. In mutants for the worm netrin homologue Unc6, sensory axons failed to project ventrally and motor neurons fail to project dorsally. This result suggested that:
(a) Unc6 can repel neurons as well as attract them.
(b) Unc6 and netrin have conserved roles as well as sequences.
(c) sensory neurons and motor neurons somehow interpret the Unc6 signal differently.
(d) All of the above
(e) None of the above

Question 8

Semaphorin receptors (called plexins) promote growth cone collapse via the small GTPase RhoA. How is this most likely to be accomplished?
(a) Activation of a RhoA GAP
(b) Activation of a RhoA GEF
(c) Inhibition of a RhoA GEF
(d) Phosphorylation of RhoA
(e) Ubiquitinylation of RhoA

Question 9

Which experiment first demonstrated the sufficiency of competing ocular inputs to produce spatial segregation in the brain?

Question 10

Temporal and nasal RGC axons behave very differently in the stripe assay with alternating anterior and posterior tectal membranes, as seen in Figure Q5-4. Figure Q5-4
A. What possible interpretations can be drawn from the selective growth of temporal RGC axons in this assay?
B. What possible interpretations can be drawn from the indiscriminate growth of nasal RGC axons in this assay?

Question 11

When Sperry and colleagues ablated the posterior (temporal) RGCs, the remaining anterior (nasal) RGCs projected to the posterior tectum. Is this definitive evidence that these neurons are programmed early in development to project only to that part of the brain? Briefly explain your reasoning.

Question 12

Surprisingly, nasal axons mistarget along the A-P axis in ephrin-A5 knockout mice. In which cells is ephrin-A5 necessary for normal nasal axon targeting?

A) In the posterior tectum, via forward signaling
B) In the anterior tectum, via forward signaling
C) In the nasal RGC axons, via reverse signaling
D) In the nasal RGC axons, via forward signaling
E) In the temporal RGC axons, via reverse signaling

Question 13

Expressing EphA3 in Islet2⁺ RGCs:
(a) provided additional support for the competition model.
(b) demonstrated that temporal axon A-P targeting depends on absolute and not relative levels of EphA3.
(c) demonstrated that temporal axon A-P targeting depends on relative and not absolute levels of EphA3.
(d) a and b
(e) a and c

Question 14

Based on neural explant assays, netrin behaves as a:
(a) attractive short-range cue.
(b) repulsive short-range cue.
(c) attractive long-range cue.
(d) repulsive long-range cue.
(e) c and d

Question 15

Humans have a much greater degree of binocular vision than mice. Which of the following is/are also very likely to be true of humans?
(a) More RGCs express EphB1 than in mice.
(b) Fewer RGCs express EphB1 than in mice.
(c) Expression of Zic2 in the retina is more restricted than in mice.
(d) More RGCs cross the midline than in mice.
(e) b, c, and d

Question 16

A single cortical neuron that receives a score of 4 on the ocular dominance scale (which ranges from 1-7) receives information from: (Select all that apply.)
(a) one eye only.
(b) the temporal parts of both eyes.
(c) the temporal part of one eye and the nasal part of the other eye.
(d) LGN neurons in either the ipsilateral or contralateral layer only.
(e) LGN neurons in both the ipsilateral and contralateral layers.

Question 17

RGC axon segregation into ipsilateral vs. contralateral layers in the LGN:
(a) is genetically determined prior to neuronal activity.
(b) is disrupted by asynchronous activity in the two eyes.
(c) requires cholinergic input from amacrine cells.
(d) b and c
(e) All of the above

Question 18

Temporal RGC axons exhibited selectivity in the stripe assay when:
(a) posterior membranes were treated with PI-PLC.
(b) posterior membranes were heat-inactivated.
(c) anterior membranes were heat-inactivated.
(d) purified ephrin-A5 was laid down in alternating stripes.
(e) c and d

Question 19

Fill in each of the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once.
The axon growth cone contains two prominent actin structures: _____________ are composed of bundled F-actin, whereas _____________ are a meshwork of branched F-actin. Many axon guidance cues affect the actin cytoskeleton through their receptors and downstream effectors such as the _____________ Rho, Rac, and Cdc42. These molecules are activated by _____________ and inactivated by _____________. For example, in the context of ephrin-A to EphA _____________ signaling, a GEF called ephexin was shown to mediate growth cone _____________ by linking the EphA receptor to RhoA.
collapse guanine nucleotide exchange factors (GEFs)
filopodia lamellipodia
forward reverse
G-protein-coupled receptors (GPCRs) small GTPases
GTPase activating proteins (GAPs) stabilization

Question 20

Both RGCs and LGN neurons are glutamatergic. If their target cells receive isolated action potentials prior to birth:
(a) only NMDA receptors will be activated.
(b) NMDA receptors will be unblocked but not activated.
(c) both AMPA and NMDA receptors will be activated.
(d) synapses between presynaptic axons and postsynaptic target cells will be strengthened.
(e) a and d

Question 21

Mosaic analysis studies have demonstrated that:
(a) The product of the Boss gene is required in the future R7 cell to determine R7 cell fate.
(b) The product of the Sevenless gene is required in the future R7 cell to determine R7 cell fate.
(c) the product of the Sevenless gene is required in the R8 cell to determine R7 cell fate.
(d) the product of the Sevenless gene acts cell nonautonomously to determine R7 cell fate.
(e) All of the above

Question 22

Which of the following general principles can be gleaned from developmental studies of the visual system in vertebrates?
(a) Connection specificity that distinguishes discrete cell types is more likely to be determined by molecular cues.
(b) Connection specificity that chooses between similar cells tends to involve neuronal activity and competition.
(c) Initial targeting by neuronal processes tends to be activity-independent.
(d) Refinement of neuronal processes tends to be activity-dependent.
(e) All of the above

Question 23

The signal from R7 that induces Rh5 expression in R8 is as yet unknown. What ommatidial phenotypes would be expected of a loss-of-function mutant for the gene encoding this signal?
(a) All R7 cells would express Rh3.
(b) All R7 cells would express Rh4.
(c) All R8 cells would express Rh5.
(d) All R8 cells would express Rh6.
(e) Both b and d

Question 24

Both ephrins and cholinergic retinal waves appear to be necessary for normal formation of retinotopic maps in the:
(a) superior colliculus.
(b) LGN.
(c) primary visual cortex.
(d) a and b
(e) a, b, and c

Question 25

Which of the following are required for retinal lamina-specific dendritic targeting by RGCs?
(a) Neurotransmission from bipolar cells
(b) Homophilic cell adhesion proteins
(c) Semaphorins and their receptors
(d) b and c
(e) All of the above

Question 26

What are the two major types of mechanisms used for wiring the nervous system? Give a specific example of each one.?

Question 27

In the Drosophila melanogaster compound eye:
(a) photoreceptors R1-R6 carry information about motion directly to the medulla.
(b) photoreceptors R7 and R8 form synaptic connections in the lamina.
(c) all ommatidia lacking R8 cells will also lack R7 cells.
(d) all ommatidia lacking R7 cells will also lack R8 cells.
(e) all ommatidia lacking R7 cells will be unable to detect blue/green light.

Question 28

Receptors of attractive cues in axon guidance and targeting include:
(a) plexins.
(b) Frazzled.
(c) cadherins.
(d) b and c
(e) All of the above

Question 29

Genetic loss- and gain-of-function mosaic analysis was used to elucidate the roles of several proteins in medulla layer-specific targeting.
A. What outcome(s) would one expect in R7 vs. R8 cells from the experimental misexpression of Frazzled specifically in R7 cells?
B. What outcome(s) would one expect in R7 vs. R8 cells from a mosaic experiment in which Senseless was removed from a presumptive R7 cell?

Question 30

What is the experimental evidence that reception of information from single whiskers by stellate neurons requires cell-autonomous glutamatergic reception?

Question 31

Place the following events in chronological order.
A. Expression of Spineless in R7 cells
B. Expression of Boss in R8 cells
C. Expression of rhodopsins in R8 cells
D. Induction of R7 cell fate
E. Induction of R8 cell fate

Question 32

What phenotype would be expected of a fruit fly with a mutation in the Ras gene that prevented its product from interacting with GAP1? Briefly explain your reasoning.