Lecture 17 - Circuit Construction I Flashcards

1
Q

What did the “Functionalist” Perspective theory on the organization of neural connectivity state?

A
  • The brain is a diffuse network of connections with little selectivity of circuits.
  • “No complication of separate and insulated reflex arcs, each of which is conceived as giving a one-to-one relation between stimulus and response, and no interconnection of such arcs by elaborate switchboard devices can conceivably yield the type of behaviour we actually find in higher vertebrates. The mechanisms of traditional reflexology seem hopelessly inadequate.” (Herrick, 1930)
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2
Q

True or False?:

Ramon y Cajal found that brain wiring is patterned and that patterning is acquired through specific properties of neurons.

A

True

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3
Q

What happened to Phineas Gage? What did this tell neuroscientists at the time?

A

Phinease Gage suffered an accident while working on a railroad in which a railroad spike went right through his head. The spike impaired his decision-making and social cognition function. This implied that there were specific regions of the brain responsible for different tasks.

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4
Q

Who was (among) the first to provide direct experimental evidence that specific connection imparted specific functions?

A

Roger Sperry

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5
Q

What were the 3 basic principles of Sperry’s Chemoaffinity Hypothesis?

A
  1. Neurons differ from one another.
  2. Differences between neurons are imparted by biochemical tags.
  3. Difference are put in place early in development (prior to circuitry formation).
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6
Q

What happened in Sperry’s famous “eye rotation” experiment? What does this tell us?

A

Sperry rotated a frog’s eye around such that dorsal became ventral and ventral became dorsal. After the optic nerve healed, the frog was unable to catch any flies put in proximity to it; it kept moving the wrong way. This tells us that every neuron in the tectum has a biochemical “tag” indicating what it is visualizing and even if you flip it around, it is still coded for the region it was coded for before flipping.

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7
Q

What happened when Sperry performed surgey on a frog’s optic chiasm such that it healed crossed to its original configuration?

A

When trying to catch food, the frog shot its tounge out in the opposite direction. It showed that even on the left/right axis, there are still specific biochemical tags that differentiate the two eyes.

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8
Q

How did Sperry map the connection between the retina and the tectum?

A

He performed a tracing study by crushing parts of the optic nerve and staining the remaining neurons to see where they projected.

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9
Q

How do axons find their target?

A

A combination of + and - factors encountered along their growth path help neurons locate their target.

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10
Q

True or False?:

Central to dendrite guidance is a specialized structure at the tip known as the growth cone.

A

False

Central to axon guidance is a specialized structure at the tip known as the growth cone.

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11
Q

What is the growth cone composed of and enriched in?

A

The growth cone is composed of filopodia and lamellipodia and enriched in cytoskeletal elements, cell surface receptors, and signal transduction machinery involved in adhesion and remodeling of the cytoskeleton.

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12
Q

True or False?:

The growth cone is a static structure that disrupts its environment.

A

False

The growth cone is a highly dynamic structure that is extremely responsive to environmental influences.

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13
Q

What happens when growth cones are exposed to a graded concentration of cytochalasin?

A

Growth cones turn when exposed to a graded concentration of cytochalasin to depolymerize actin on one side. The depolymerized side will retract while the other side will continue to grow.

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14
Q

What is the difference between F-actin and G-actin?

A

G-actin is monomeric while F-actin is polymeric.

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15
Q

What are growth cone filopodium composed of?

A

F-actin

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16
Q

Suppose you have fluorescently labelled microtubules during axon extension and locally eliminate fluorescence in a portion of the axon. What will happen as the axon continues to grow? What does this tell us?

A

The bleached area of the axon will not move while labelled microtubules will be added distally. This tells us that microtubules are only built at the end of the axon.

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17
Q

What kind of substrate is preferred by growth cones?

A

Adhesive Substrates

18
Q

What will cause a growth cone to slow down on its way to its target?

A

A growth cone will slow down when it reaches a “choice point”, at which it must slow down and explore the different directions in which it may proceed.

19
Q

How do growth cones on adhesive substrates differ from growth cones on non-adhesive substrates?

A

Growth cones on adhesive substrates are flattened, have lots of filopodia, and do not move rapidly. Growth cones on less adhesive substrates are more compact, rounded, have fewer processes, and often move more quickly.

20
Q

Axon guidance relies on a balance between what two processes? What are the two types of each of these?

A

Attraction (chemoattraction and contact-dependent attraction) and Repulsion (chemorepulsion and contact-dependent repulsion)

21
Q

How do extracellular matrix molecules influence axon guidance?

A

Extracellular matrix molecules interact with integrin, which signals to kinases/other signaling molecules inside the cell which drive further signal transduction.

22
Q

How do cell-adhesion molecules (CAMs) influence axon guidance?

A

CAMs will interact with CAMs on other cells to help hold them together. When CAMs interact with other extracellular CAMs, they are able to signal to kinases/other signalling molecules inside the cell.

23
Q

How do cadherins influence axon guidance?

A

When cadherins bind with another cadherin, they signal via kinases directly to intracellular actin to change the cell shape.

24
Q

How do ephrins influence axon guidance?

A

Ephrins signal via Eph receptors, which signal via Rho/GAPs to act on actin. The ephrin will act on kinases/other signaling molecules in its bound cell. This signal is bidirectional and acts on both cells involved.

25
Q

How do netrin and slit influence axon guidance?

A

Netrin interacts with DCC and Unc5 while slit interacts with robo. All of those go on to interact with Rho/GAPs, which interact with actin.

26
Q

What is the effect of netrins dependent upon?

A

cAMP Levels

27
Q

When is netrin attractive and when is it repulsive?

A

Netrin is attractive when acting upon DCC homodimers and repulsive when acting upon DCC-Unc5 heterodimers.

28
Q

What is the signal that attracts dorsal comissural interneurons towards the floorplate? How was this proven?

A

Netrin

This was proven by placing a netrin-expressing cell line beneath the dorsal neural tube and observing the interneurons project axonal growth towards the netrin cells.

29
Q

True or False?:

Netrin acts as a long-range attractive signal.

A

True

30
Q

True or False?:

Growth cone attraction is necessary and sufficient for axon guidance.

A

False

Growth cone repulsion is also important for axon guidance.

31
Q

How does netrin cause trochlear motor neurons to extend dorsally?

A

The floorplate secretes netrin, which acts repulsively on trochlear motor neurons, driving them dorsally.

32
Q

What drives commissural interneurons to cross over the floorplate?

A

As the neurons approach the floorplate, netrin stops being attractive and slit starts being repulsive. It pushes the axons away from the floorplate, causing them to cross over.

33
Q

What happens in a Drosophila mutant that does not contain robo?

A

The commissural interneurons will approach the floorplate but then not be repelled away (because slit can’t act on the cells). In consequence, the neurons cyclically approach the floorplate and then retreat, giving rise to their roundabout (robo) name.

34
Q

How do semaphorins influence axon guidance?

A

Semaphorins repulsively act on plexin and neuropilin, which interact with actin via Rho/GAPs.

35
Q

What process associated with axon guidance is pictured below?

A

Contact-Dependent Repulsion

36
Q

How can a cell’s polarity be developed by secreted signals?

A

An efferent axon can be repulsed by signals while the attraction of an apical dendrite and further branching of the dendrites can be induced by different signals acting on a gradient of receptors on the cell.

37
Q

What would happen to the dorsal root ganglia (left) if the cells on the right produce a secreted form of Sema3A?

A

The axons on the DRG will be repulsed.

38
Q

Why does the temporal part of the retina connect to the anterior of the tectum while the nasal part of the retina connect to the posterior of the tectum?

A

Nerves starting in the temporal end of the retina have a high sensitivity to repulsive ephirin found in the tectum. They are unable to make it to the posterior end of the tectum, as the repulsive force is too strong. Nerves starting in the nasal part of the retina have a low sensitivity and are able to tolerate more of this repulsive force, allowing them to project into the posterior of the tectum.

39
Q

True or False?:

Shh and BMPs cooperate with Netrin to guide commissural axons. Axons are guided up an attractive Shh gradient and down a repulsive Wnt4 gradient.

A

False

Shh and BMPs cooperate with Netrin to guide commissural axons. Axons are guided up an attractive Wnt4 gradient and down a repulsive Shh gradient.

40
Q

In which direction does the Wnt4 and Shh gradients drive commissural axon growth (after crossing the floorplate)?

A

Anteriorly