Module 1 Lecture 5: Target Selection

Question 1

topographic map

Answer 1

ordered projection of a sensory surface (eg skin or retina) or an effector system (eg musculature) to regions in the CNS

Question 2

defining feature of topographic maps

Answer 2

neighbor relations in the sensory surface are preserved in target area

Question 3

where does optic topographic mapping occur

Answer 3

back of retina, superior colliculus, tectum, lateral geniculate nucleus, visual cortex

Question 4

chemoaffinity hypothesis

Answer 4

2+ cytochemical gradients in the retina and tectum stamp the RGCs and target with matching chemical codes (identity) to establish the observed mapping

Question 5

roger sperry’s experiment

Answer 5

1. cut the optic nerve of an amphibian
2. rotate the eyeball 180 degrees
3. wait for regeneration
4. assay for visual behavior

Question 6

result of roger sperry’s experiment

Answer 6

animals behave as if their world is turned around
- never learn

Question 7

where does the nasal retina map to

Answer 7

posterior tectum

Question 8

where does posterior retina map to

Answer 8

anterior tectum

Question 9

what causes topographic mapping between the retina and the tectum

Answer 9

built-in, anatomical features, rather than experience

Question 10

first step of Bonhoeffer’s experiment

Answer 10

prepare cell membrane from anterior and posterior tectum (chick)

Question 11

second step of Bonhoeffer’s experiment

Answer 11

deposit membrane in very thin alternating stripes

Question 12

third step of Bonhoeffer’s experiment

Answer 12

test how retinal axons across the nasal temporal axis grow on stripes

Question 13

fourth step of Bonhoeffer’s experiment

Answer 13

treat posterior membranes with protease or PI-PLC (phsphatidylinositol-specific phospholipase C), which cleaves PI

Question 14

results of Bonhoeffer’s experiment

Answer 14

1. nasal axons have no preference
2. temporal axons prefer anterior membrane
3. preference lost with membrane treatments; consistent with repulsive influence from posterior membranes

Question 15

conclusion fo Bonhoeffer’s experiment

Answer 15

glycosylphosphatidylinositol (GPI)-linked cell surface protein enriched in the posterior tectum triggered repulsion of temporal axons

Question 16

what does ephrin-5A do

Answer 16

causes growth cone collapse

Question 17

where is ephrin-5A found

Answer 17

enriched in the posterior tectum

Question 18

two types of ephrins

Answer 18

1. ephrin-A: GPI linked
2. ephrin-B: transmembrane domain
   - 8 ephrins in mammals
   - As bind As, Bs bind Bs

Question 19

what are ephs

Answer 19

receptor tyrosine kinases; important to cell proliferation and survival, as well as migration and axon guidance

Question 20

what kind of signaling do ephrins do

Answer 20

1. forward signaling (ephrin:Eph)
2. reverse signaling (Eph:ephrin, the ephrin expressing cell responds)
3. bidirectional signaling: both cells respond

Question 21

what is the gradient in the tectum

Answer 21

posterior to anterior high-to-low ephrin-A5 and -A2

Question 22

what is the gradient in the retina

Answer 22

temporal to nasal high-to-low EphAs

Question 23

how does the posterior tectum affect axons from the temporal retina

Answer 23

repelled

Question 24

relationship between temporal retina axons and the posterior tectum with ephrin-A2, A5 double mutants

Answer 24

they can target the posterior tectum

Question 25

if topographic mapping is based on repulsion, then how do nasal axons avoid the anterior tectum?

Answer 25

counter gradients and reverse signaling: - tectum: A-to-P high-to-low EphAs - retina: N-to-T high-to-low ephrin-A5 - axons from nasal retina are repelled from anterior tectum due to ephrin reverse signaling

Question 26

what system guides the axon maps from the retina to the superior colliculus and the dorsal lateral geniculate nucleus, from the dorsal lateral geniculate nucleus to visual cortex, and visual cortex back to the previous stuff?

Answer 26

EphA and ephrin-A counter gradients

Question 27

do counter gradients of EphB and ephrinBs exist, and what do they do?

Answer 27

yes, exist alongside non-graded expression in the D-V axis of the retina and the medial-lateral axis of the superior colliculus

Question 28

what do Cajal-Retzius cells express

Answer 28

multiple Eph receptors and ephrin ligands

Question 29

wildtype Cajal Retzius cells vs EphB1/B2/B3 triple mutants

Answer 29

wildtype cells display contact dependent repulsion; EphB1/B2/B3 triple mutants cluster

Question 30

what is required for wildtype Cajal-Retzius cell distribution

Answer 30

contact-dependent repulsion

Question 31

hypotheses for why the CNS is built up in layers

Answer 31

1. protect info --> minimize entropy 2. minimize energy

Question 32

what happens if Robo2 is mutated

Answer 32

RGC axons spread across depth of tectum; some project to multiple layers and have diffuse terminal processes

Question 33

what happens if Slit is knocked down

Answer 33

same as if Robo2 is mutated

Question 34

what happens if Slit is overexpressed

Answer 34

same as if Robo2 is mutated

Question 35

what happens if Collagen IV is mutated

Answer 35

no Slit and RGCs looks same as if Robo2 is mutated

Question 36

where does Slit protein accumulate

Answer 36

in the basement membrane, under the skin cells - stays there by sticking to Collagen IV

Question 37

steps for development of retina

Answer 37

- optic vesicles extend from neural tube - turn into cups (now two layers) - overlying ectoderm thicken and invaginates; will become the lens

Question 38

where does most computation occur in the retina, and what types

Answer 38

inner plexiform layer - visual features such as light on/off, edges, colors, direction of motion

Question 39

where does the vertebrate retina originate from

Answer 39

pseudostratified neuroepithelium - retinal progenitor cells (RPCs) are connected to both apical and basal laminae and divide preferentially at the apical domain

Question 40

is the retina built inside-out?

Answer 40

no

Question 40

recoverin function

Answer 40

marks photoreceptors

Question 40

what kinds of gradients of development exist in the retina

Answer 40

spatial, in addition to temporal - central retina develops ahead of peripheral retina

Question 40

how do bipolar cells target to the OPL and IPL

Answer 40

by retracting the apical and basal processes of retinal progenitors

Question 40

where do bipolar dendrites form

Answer 40

at the BPL

Question 41

where do bipolar axons form

Answer 41

at the IPL

Question 42

order of addition to IPL

Answer 42

1. amacrine cells (2nd born) 2. retinal ganglion cells (1st born) 3. bipolar cells (last born)

Question 43

where do tyrosine hydroxylase (TH) - expressing dopaminergic amacrine cells predominantly stratify

Answer 43

within the S1 sublamina of the IPL in wild-type

Question 44

where are Sema5A and 5B expressed

Answer 44

in the developing mouse outer nucleoblast layer (ONBL)

Question 45

what happens in Sema 5B and 5A/5B mutants

Answer 45

dopaminergic amacrine neurons, which normally have projections in the S1 layer of the IPL, mis-target into the INL

Question 46

where do melanopsin expressing intrinsically photosensitive RGCs predominantly stratify

Answer 46

in the S1 sublamina of the IPL in wild-type

Question 47

what is the working model of targeting to the IPL

Answer 47

- during early retinal development, class 5 semaphorins are expressed by cells in the ONL - contact with Sema5-expressing tissues biases the extension of neurites, such as those of tyrosine hydroxylase-expressing dopaminergic amacrine cells (DACs, 'TH') - following initial redirection, DAC neurites extend into the OFF layers of the IPL

Question 48

characteristics of PlexinA4 and Sema6A proteins

Answer 48

expressed in a complementary pattern in the developing inner plexiform laeyr

Question 49

ipRGCs and DACs relationship

Answer 49

synaptic partners (make synapses together)

Question 50

what happens in PlexA4 mutants

Answer 50

both ipRGCs and DACs extend far deeper into the IPL - new extensions appear to overlap

Question 51

what happens in Sema6A mutants

Answer 51

same as in PlexA4 mutants

Question 52

what cells express PlexA4

Answer 52

DACs, not ipRGCs

Question 53

Sema6A functioning in deeper layers of the IPL

Answer 53

keeps PlexA4 expressing DAC processes confined to the S1 layer

Question 54

characteristic of ipRGC targeting

Answer 54

may be dependent on its direct interactions with DAC processes

Question 55

class 5 semaphorins function

Answer 55

direct the neurites of DACS ('TH') to the IPL

Question 56

ipRGC ('M1') targeting to the S1 layer of the IPL characteristic

Answer 56

may be guided by its interactions with DACs

Question 57

examples of homophilic binders

Answer 57

Cntn2,3,4, Sdk1, Sdk2, Dscam, DscamL - do not interact with each other

Question 58

what does RNAi-mediated knockdown of Cntn2 cause

Answer 58

disruption of Skd1 expression layer

Question 59

CAM-code model of IPL layer targeting

Answer 59

each synaptic lamina has a unique combination of homophilic cell adhesion molecules, encoded by related genes of the immunoglobin superfamily - misexpression and knockdown experiments show that these cell adhesion molecules can be sufficient and necessary for targeting synaptic terminals to specific sublaminae

Question 60

what does ONL stand for

Answer 60

outer nuclear layer

Question 61

what does OPL stand for

Answer 61

outer plexiform layer

Question 62

what does INL stand for

Answer 62

inner nuclear layer

Question 63

what does IPL stand for

Answer 63

inner plexiform layer

Question 64

what does GCL stand for

Answer 64

ganglion cell layer