Axon Guidance II Practice Flashcards

Comprehensive practice flashcards covering axon guidance stages, topographic mapping, Roger Sperry's experiments, chemoaffinity hypothesis, and connection refinement mechanisms.

How do growth cones exit the retina and enter the optic nerve?

They are pushed away from the retina by the repellent Slit and pulled toward the base of the optic nerve by the attractant Netrin.

What role do Semaphorins play as axons travel along the optic nerve?

They act like guardrails to constrain the axons within the nerve pathway.

What decision must axons make at the optic chiasm?

They must choose whether to stay on the same side (ipsilateral) or cross over to the other side of the brain (contralateral).

Which receptor is expressed by ipsilateral growth cones at the optic chiasm?

EphB1.

Which ligand at the optic chiasm repels EphB1-expressing axons?

Ephrin B2.

Why do contralateral axons ignore the Ephrin B2 repellent at the chiasm?

They do not express the EphB1 receptor.

Which receptor and cell adhesion molecule are expressed by contralateral axons?

Plexin A1 and NrCAM.

Which Semaphorin is expressed at the optic chiasm to interact with contralateral axons?

Sema6D.

How does the presence of NrCAM change the response of contralateral axons to Sema6D?

It contextually transforms the Sema6D repellent into a powerful attractant, pulling axons across the chiasm.

What protein do contralateral axons physically grip to migrate along the forebrain toward the tectum?

Laminin, which is an extracellular matrix (ECM) protein.

What happens to the sensitivity of axons toward Semaphorins after they cross the midline and reach the forebrain?

They turn off NrCAM, causing Semaphorins to return to being repellents that, along with Slit, keep them channeled on the correct path.

How do axons successfully navigate long, complex distances?

They break the journey into short, independent segments and dynamically swap receptors at different waypoints.

Where do retinal ganglion cells project in frogs?

Directly to the optic tectum in the dorsal forebrain.

In mammals, what are the two main projection targets for retinal neurons?

The lateral geniculate nucleus (LGN) of the thalamus and the superior colliculus (the anatomical equivalent of the tectum).

What is the definition of a topographic map?

A $2$-dimensional representation in the brain that strictly preserves the spatial topology of incoming neurons, maintaining a point-to-point correspondence.

How does the nasal-temporal axis of the retina map onto the tectum?

It maps directly onto the anterior-posterior axis of the tectum.

Which region of the retina projects to the anterior tectum?

The temporal side.

Which region of the retina projects to the posterior tectum?

The nasal side.

In Roger Sperry's experiment, what happened to existing axons after the optic nerve was severed?

The existing axons naturally degenerated.

What occurred when Sperry rotated the frog's eye $180^{\circ}$?

The regenerating retinal neurons navigated back to their exact original target sites in the tectum, ignoring the new orientation.

Why was the frog's vision permanently inverted after the eye rotation experiment?

The eye was physically upside down and backward, but the wiring to the brain remained exactly the same as before the rotation.

What did the frog's hunting behavior after eye rotation prove about regenerating axons?

They followed strict positional instructions rather than adapting to their new functional reality.

What occurs initially if the posterior half of the tectum is removed (Map Compression)?

The temporal axons hit the anterior tectum normally, but the nasal axons go as far as they can until they hit a dead end.

How does the map regulate after the partial removal of the tectum?

The projecting axons compress and redistribute themselves to recreate the full map pattern on the remaining smaller piece of tissue.

What is Map Expansion in the context of removing half of the retina?

If the nasal retina is removed, the remaining temporal axons initially project only to the anterior tectum but eventually expand to cover the entire tectum.

Define the Chemoaffinity Hypothesis proposed by Sperry.

Each tectal cell carries a chemical 'identification tag' and growing retinal ganglion cell terminals have 'complementary tags' to seek specific locations.

In the chemoaffinity hypothesis, what do the 'tags' actually represent?

Gradients in expression of guiding molecules in the tectum and corresponding receptors in the growth cones.

Who performed the Stripe Assay experiment?

Frederich Bonhoeffer.

What was the purpose of the Stripe Assay?

To investigate the molecular mechanisms of axon guidance in the retinal-tectal topographic map by testing membrane preferences.

According to the Stripe Assay, what is the preference of temporal retinal axons?

They overwhelmingly prefer to migrate along anterior tectal membrane stripes.

According to the Stripe Assay, what is the preference of nasal retinal axons?

They prefer to migrate along the posterior tectal membrane stripes.

Which guidance ligands drive topographic mapping in the retinotectal system?

Ephrins, specifically Ephrin A2 and A5.

Describe the distribution of Ephrin ligands across the tectum.

It is a gradient along the anterior-posterior axis, with low concentration in the anterior and high concentration in the posterior.

What is the receptor for Ephrin expressed by retinal growth cones?

EphA3.

Describe the gradient of EphA3 expression across the retina.

It is highly concentrated in the temporal retina and very sparse in the nasal retina.

Why does a temporal axon stop its migration in the anterior tectum?

Because it has many EphA3 receptors, it is highly sensitive to the repellent Ephrin and finds even low concentrations in the anterior region overwhelming.

Why can a nasal axon travel far into the posterior tectum?

It has very few receptors, making it less sensitive to the repellent Ephrin, so it requires the high concentration in the posterior to stop its migration.

Where do axons from the middle of the retina settle in the tectum?

In the middle of the tectum, due to intermediate receptor levels.

How is the vertical (dorsal-ventral) 2D map built?

Using the same gradient-matching logic as the A-P axis, but with a different set of Ephrin ligands and Eph receptors.

What is the result of a double knockout of Ephrin A2 and A5 in mice?

The guidance system breaks down, and axons scatter randomly across the anterior-posterior axis of the tectum.

What promoter was used in the transgenic mouse experiment to overexpress EphA3?

The Brn3c promoter.

What is unique about the Brn3c promoter in the retina?

It is only active in a randomly scattered subset of retinal cells.

What happens when tracing axons from a single position in the transgenic EphA3 overexpression retina?

The axons split and project to two distinct locations in the tectum.

In the transgenic experiment, which population of cells projects more anteriorly?

The population expressing higher levels of EphA3 (normal + transgene) because they are overly sensitive to the repellent signal.

Why must the topographic map in frogs remain active and dynamic?

Because the animal continues to grow significantly, meaning the eye adds new neurons and the tectum adds new target cells.

How do regenerating axons rebuild original connections in Sperry's experiments?

They hijack the active, continuous re-evaluation system that normally maintains the map during natural growth.

What term describes the initial connections made by retinal axons that are broad and overlapping?

Fuzzy.

Which process prunes away diffuse connections to create a concentrated, sharp map?

Synapse stabilization and elimination.

What mechanism allows the map to compress after half the tectum is removed?

The remaining tectum senses the lost tissue and actively regenerates a full, scaled-down Ephrin gradient across the remaining half.

Why are neurotrophins important in the nervous system?

They assist with cell survival/death, neural process growth/retraction, fine-tuning connectivity, and synapse stabilization/elimination.

What did the chamber experiment regarding NGF prove about neuronal survival?

Cell survival is dictated by target-derived concentrations of NGF, as the survival signal is retrograde transported from the axon tips to the cell body.

How does local neurite growth react to the removal of NGF in its specific chamber?

Local neurites regress, retract, and lose their branching.

What is the effect of having NGF present in a distal chamber even if it is absent from the cell body chamber?

The neuron will survive globally, and the distal neurites will continue to grow and branch locally.

What is the final result of synapse stabilization and elimination in the topographic map?

The initial fuzzy map is transformed into a sharpened, highly concentrated, and non-overlapping projection pattern.

What receptor is linked with the choice of contralateral axons at the chiasm to detect Semaphorins?

Plexin A1.

What is the role of NrCAM when it is co-expressed with Plexin A1?

It changes the growth cone's interpretation of Sema6D from being a repellent to an attractant.

Which physical landmarks are described as the 'crossroads' of axon guidance in the visual system?

The optic chiasm.

What direction does the temporal retina normally project onto the tectum?

Anterior.

What direction does the nasal retina normally project onto the tectum?

Posterior.

What are the two axes across which a complete retinal map is created?

The nasal-temporal axis and the dorso-ventral axis.

What happens to axons when they reach a 'dead end' in a surgically reduced tectum before regulation?

They go 'as far as they can' until they hit the tissue boundary.

How long does it take for a map to regulate following the removal of half the retina?

A few weeks.

In the Stripe Assay, what specific material is used to create the tracks?

Extracted cell membranes from the anterior and posterior regions of the optic tectum.

Which experiment proves that topographic mapping is regulated by relative sensitivity rather than absolute chemical values?

The transgenic EphA3 overexpression experiment.

What is the ligand distribution for the D-V axis mapping?

A gradient distribution across the target tissue, similar to the A-P axis.

Which molecules are identified as the chemical tags Sperry theorized?

Repulsive Ephrin gradients.

In the optic nerve, what prevents axons from wandering off the path?

Semaphorins acting as guardrails.

What happens to the mapping of neighbors between the eye and the brain?

Neighbors in the eye stay neighbors in the brain.

Which structure in mammals corresponds to the optic tectum of frogs?

The superior colliculus.

What is the secondary target for retinal axons in mammals?

The lateral geniculate nucleus (LGN).

Where do axons go after arriving at the LGN in mammals?

On to the visual cortex.

Does the topographic map apply to the LGN in mammals?

Yes, even though the primary target is the LGN, the same mapping principles apply.

Is the LGN the anatomical equivalent of the tectum?

No, the superior colliculus is the anatomical equivalent.

What is retrograde transport in the context of neurotrophins?

The backward movement of survival signals from the axon tips at the target to the cell body.

What happens to neuronal connectivity during 'fine-tuning'?

Connections are refined through synapse stabilization and the elimination of redundant or fuzzy synapses.

Why is the chemoaffinity hypothesis considered relative rather than absolute?

Because tags are labels of relative position in a developmental field (gradients) rather than absolute labels for individual cells.

If you remove the nasal half of the retina, how do the temporal axons respond after regulation?

They spread out to utilize the whole tectum while maintaining their relative topographic order.

What is used to trace RGC projections in mouse experiments?

Lipophilic fluorescent dyes.

How do researchers create 'two populations' of cells at one location in the transgenic experiment?

By using a Brn3c promoter that is only active in a random scattered subset of retinal cells.

What causes the 'split' projection result in the over-expression study?

Cells at the same location have different receptor levels, leading to different stopping points along the repellent gradient.

What allows a growth cone to change its sensitivity to the same cues along its journey?

The dynamic swapping of receptors at various waypoints.

What is rostral-caudal in the context of the tectum?

Anterior-posterior.

Which specific axons settle in the posterior tectum?

Nasal axons.

Which protein provides a physical surface for migration of contralateral axons up the forebrain?

Laminin.

What is the primary sensory result of Sperry's eye-rotation experiment?

Permanent inversion of vision causing the frog to hunt in the wrong direction.