Lecture 7 - Synaptogenesis I

Question 1

What are the three critical point when considering the formation and elimination of synapses?

Answer 1

1. recognition of synaptic targets is specific
2. Principles of synaptic differentiation are revealed at the NMJ
3. Some synapses are eliminated after birth

Question 2

What is the key idea to consider when thinking about how the growth cone recognizes synaptic targets specifically?

Answer 2

Want to get a critical idea about how does the growth cone know where to make a synapse and how does it transform into a presynaptic terminal and how does the postsynaptic terminal differentiate into a postsynaptic compartment

Question 3

What are the 3 key processes that drive synapse formation?

Answer 3

1. axons make choices among many potential postsynaptic targets (how does the decision get made and how does it pick which possible target to make a synapse with post axon guidance)
2. What portion of the axon that contacts the target cell differentiate into a presynaptic nerve terminal and the domain of the target cell contacted by the axon differentiated into a specialized postsynaptic apparatus
3. synapses continue to mature and model

Question 4

What shapes synaptic structure and function?

Answer 4

interplay of molecular programs and neural activity

Question 5

What strategies does nature use to cause synaptic specificity?

Answer 5

distinct molecules which are influenced by activity drive this process

Question 6

What promotes selective synapse formation?

Answer 6

recognition molecules

Question 7

What was the evidence the proves there was molecular recognition in synaptic specificity?

Answer 7

preganglionic MNs regenerate selective connections with sympathetic neuronal targets

Question 8

Where do axons of preganglionic MNs from T2 project to?

Answer 8

the eye muscles

Question 9

Where do axons of preganglionic MNs from T4 project to?

Answer 9

innervate the blood vessels of the ear

Question 10

Even though preganglionic MNs from T2 and T4 are intermingled in the ganglion where do they form synapses?

Answer 10

in their selective synapgtic targets so they synapse with neurons that form synapses on synaptic targets

Question 11

If you cut the axons in T2 and T4 and allow then to regenerate what will you see?

Answer 11

that they form synapses with the same synaptic targets - in adults there are similar segment specific patterns of connectuvey that are reestablished through reinnervation - support that synapse formation is selectuve

Question 12

What two models were used to study synaptic targeting?

Answer 12

retinal ganglion neurons in the visual system and olfactory receptor neurons in the olfactory bulb

Question 13

What type of synpases do retinal ganglion neurons form?

Answer 13

layer specific synapses - functinally distinct neuorns form specific connections to postsynaptic cells

Question 14

Where do retinal ganglion cells project to and how do they project to this region?

Answer 14

they project to the optic tectum in the midbrain and have specific layers which they synapse onto

Question 15

Where do the dendrites of retinal ganglion cells receive input from?

Answer 15

–interneurons (bipolar and amacrine cells) in a region subdivided into 10 sublaminae in the inner plexiform layer in the eye or retina

Question 16

Where do specific subsets of internueons whcih set projections to the dendrites of rgcs in the eye in the inner plexiform layer and the rgcs which send inputs to the optic tectum send their projections to and arborize and synapse?

Answer 16

onto just one layer and these laminae specific connections determine which visual stimuli actuvate which rgcs

Question 17

What are expressed in different subsets of retinal ganglion neurons?

Answer 17

immunoglbulin super family adhesion molecules - i.e. dscam, sdk1, sdk2, dscaml

Question 18

What rule do these immunoglobulin recognition molecules follow for the RGCS?

Answer 18

like like rule of homotypic interactions

Question 19

If you force a RGC to express dscam instead of what it originally did where will it go to?

Answer 19

dscam because it is solely depedndent on the adhesion molecule

Question 20

If you KO an immunoglobulin adhesion molecule where will the RGC innervate?

Answer 20

all layers at random

Question 21

What do olfactory receptors influence?

Answer 21

the targeting of sensory axons to discrete glomeruli in the olfactory bulb

Question 22

How many receptors do the olfactory sesnory neurons express?

Answer 22

one and only one

Question 23

What are the receptors in olfatcory sensory neurons?

Answer 23

GPCRs and they mediate smell so a thousand receptors which each mediate smell different smell through binding various odors and once one receptor type is expressed the olfactory neuron will shut down other genes in response to a particular smell and they are distributed all over the nose

Question 24

Where do all of the same type of olfactory neuron project to?

Answer 24

the same glomerulus in the olfatcory bulb

Question 25

What is the glomerulus?

Answer 25

the projections of the sensory olfactory neuorns synapsing onto secondary motor neurons which receuve the olfactory info and project to the bran and cause smell associations

Question 26

Where are olfactory sensory neurons found that express the same receptor?

Answer 26

distributed sparsely throguhout the nose and project to glomeruli in the olfatcoyr bulb

Question 27

What happens in a mouse mutant in which an odorant receptor gene is deleted?

Answer 27

-the neurons that would have expressed the gen send their axons to other glomeruli for the receptor genes the neurons now express because the KO gene is no longer suppressing the expression of the other genes

Question 28

What happens if you knockout all olfactory receptor genes in an olfatciry sensory neuron?

Answer 28

it will still find a unique glomeruli which means there are other guidance cues involved

Question 29

What happens in olfactory sensory neurons if you do an olfactory receptor swap where you take a green receptor neuron and force it express blue and why?

Answer 29

-it will innervate a completely different glomeruli from both the green and blue receptor neurons - this is due to the fact that the cell TF fate told it express a certain number of ioon channels so when the odorant revceptor gene is changed they can aquire adifferent repnse to the same stimulus and the cell can be more or less exitable depndening on its previously determined TF number of channels expressed

Question 30

How come when in odrant receptor gene is repleced by another in a set of olfatciry sensory neurons their axons porject to new glomerulus?

Answer 30

activity is likely changed in these neuron given combo of receptor expressed and specialized ion channels influencing the nature and level of expression of axonal guidance and recognition molecules

Question 31

What are the two main jobs of olfactory sensory neurons?

Answer 31

1. determine a neurons responsiveness to specific odorants
2. also help the axon to form appropriate synapses on target neurons

Question 32

What have recognition molecules been found to do in the interactions of olfactory axons?

Answer 32

found to regulate the interactions of olfactory axons with each other and with their targets

Question 33

What three decisions are need in synaptic targeting and specificity?

Answer 33

1. decision on what general tissue and brain region the synapse is going to be made - axon guidance
2. decision about what specific cell or target to make a synapse with within this region
3. final decision what subcellular region of the spcific target on which you want to make a synapse

Question 34

Where are different synaptic inputs directed to?

Answer 34

discrete domains of the postsynaptic cell

Question 35

Where doe synapses form on neurons in the cerebellum?

Answer 35

on spatially distinct subdomains of purkinje neurons

Question 36

In the cerebellum where to climbing fibers terminate?

Answer 36

on distinct regions of distal dendrites

Question 37

In the cerebellum where do inhibitory basket cells synapse onto?

Answer 37

the axon initial segment which allows for a more powerful toning down of hyperexcitabulity and allows for more direct inhibition

Question 38

What do inhibitory basket cells recognixze on the axon intial segment and what is it anchored by?

Answer 38

-IG domain proteins known as neurofascin and it is anchored by the cytoskeleton protein akyrin g
-instructs synpases to form at this region

Question 39

What happens in the cerebellum to the inhibtory basket cells if you express neurofascin in other subcellular areas?

Answer 39

the basket cell axons fail to restruct their synapse formation to the axon intial segment

Question 40

What is the role of neuronal activity if any in synapse targeting and stabilization?

Answer 40

activity refines synapses

Question 41

Is neural activity needed for basic wiring in the synaptic connections in the retina? But what does it do instead?

Answer 41

-no it is not neeed for basic wiring
-early in yoy see rough layers and dendrites trying to find their targets and see an imprecise map of RGCs and they have relatively broad distribution and with time you get more specific targeting of the dendrites in their retunal ganglion cells and

Question 42

What happens in terms of synaptic connection if you suture one eye of a cat and leave one eye open during the critical period of development?

Answer 42

-in the iopen eye the rgcs will be more refined in the inputs they receive layer wise in the sublaminae in the retina and the inner plexiform layer but in the sutured eye you will not see this refinement indicating activity causes refinement of synaptic conncetions

Question 43

What does abolishing electrucal activitry in retinal ganglion cells cause?

Answer 43

decreases the remodeling of dendritic and axonal arbors

Question 44

What controls the intial specifity of synaptic connections and what controles the sharpening of that specificity?

Answer 44

initial specificty is controlled by molecular cues and the shaerpening is controlled by activity and in the sharpening process axon terminals become refined and dendritic branches are pruned

Question 45

What is revealed at the NMJ?

Answer 45

the principles of synaptic differentiation

Question 46

What are the three types of cells at NMJ?

Answer 46

Motor neuron
muscle fiber
schwann cell or glia

Question 47

What are the characteristic metabolic molecular and electrical properties that identify muscle fibers?

Answer 47

slow or fast types

Question 48

Staining of what proteins shows different MNs innervating same type of muscle?

Answer 48

staining of myosin ATPase

Question 49

How many motor neurons innervate a muscle fiber?

Answer 49

one

Question 50

What is slow twicth muscle for?

Answer 50

long systained actifity and they fo not fatigue as much and take time to ramp up and tend to have tonic activity - 1AP/s -s teady low frequency bursts

Question 51

What is fast twitch muscle for?

Answer 51

sprinitng robust movemnt so fatigue fast and have phasic activity - 10APs/s -high frequency bursts

Question 52

What is different in MNs that connect with fast and slow twicth muslce fibers?

Answer 52

exhibit different patterns of electrical actviity

Question 53

How does the pattern of MN activity change the biochemical and functional properties of muscle?

Answer 53

-surgical cross innervation experiments demonstrate the some property of the MN helps determine whether muscle fibers are fast or slow - can convert a fast twicth musscle to slwo and slow to fast

-in rat or mouse surgically move MNs and move to other muscle and take fast MN and move to slow muscle and slow MN and take to fast muscle and the MNs maintain same activity because upstream premotor inputs drive this activity over a few days the muscles transform to the other type of muscle so muscle physiology changes meaning the myosin ATPase switches

Question 54

How does the pattern of electrical stimulation alone define functional properties of muscle?

Answer 54

-when fast twicth muslce is stimulated with a slow tonic pattern - muscle gets slow electurcal and miolecular properties same for fast to slow

-Denervate and cut the MN and use a glass pipette and have a computer do a tonic or phasic activity pattern and that is sufficient alone to change the physiology of the muscle of the slow or fast

Question 55

What does the muscle dictate for the MN?

Answer 55

the MNs whcih survive and the neurotransmitter phenotype

Question 56

How does the MN dictate the patten of the muscle?

Answer 56

can define biochemical and electriphysiological proteries of muscle like FT and ST

Question 57

What is reciprocal synaptic dialogue?

Answer 57

the muscle and neuron are talking to each other and instructing the muscle what it should become and the MN what type of neurotransmitter and whether it should survive; the pattern of activity can alone change the physiology of a muscle so if a MN dies in ALS so if you kill a tonic MN and a phasic MN innervates denervated muscle the muscle needs to acquire properties for fast muscle