Lecture 7 - Synaptogenesis I Flashcards
What are the three critical point when considering the formation and elimination of synapses?
- recognition of synaptic targets is specific
- Principles of synaptic differentiation are revealed at the NMJ
- Some synapses are eliminated after birth
What is the key idea to consider when thinking about how the growth cone recognizes synaptic targets specifically?
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
What are the 3 key processes that drive synapse formation?
- 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)
- 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
- synapses continue to mature and model
What shapes synaptic structure and function?
interplay of molecular programs and neural activity
What strategies does nature use to cause synaptic specificity?
distinct molecules which are influenced by activity drive this process
What promotes selective synapse formation?
recognition molecules
What was the evidence the proves there was molecular recognition in synaptic specificity?
preganglionic MNs regenerate selective connections with sympathetic neuronal targets
Where do axons of preganglionic MNs from T2 project to?
the eye muscles
Where do axons of preganglionic MNs from T4 project to?
innervate the blood vessels of the ear
Even though preganglionic MNs from T2 and T4 are intermingled in the ganglion where do they form synapses?
in their selective synapgtic targets so they synapse with neurons that form synapses on synaptic targets
If you cut the axons in T2 and T4 and allow then to regenerate what will you see?
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
What two models were used to study synaptic targeting?
retinal ganglion neurons in the visual system and olfactory receptor neurons in the olfactory bulb
What type of synpases do retinal ganglion neurons form?
layer specific synapses - functinally distinct neuorns form specific connections to postsynaptic cells
Where do retinal ganglion cells project to and how do they project to this region?
they project to the optic tectum in the midbrain and have specific layers which they synapse onto
Where do the dendrites of retinal ganglion cells receive input from?
–interneurons (bipolar and amacrine cells) in a region subdivided into 10 sublaminae in the inner plexiform layer in the eye or retina
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?
onto just one layer and these laminae specific connections determine which visual stimuli actuvate which rgcs
What are expressed in different subsets of retinal ganglion neurons?
immunoglbulin super family adhesion molecules - i.e. dscam, sdk1, sdk2, dscaml
What rule do these immunoglobulin recognition molecules follow for the RGCS?
like like rule of homotypic interactions
If you force a RGC to express dscam instead of what it originally did where will it go to?
dscam because it is solely depedndent on the adhesion molecule
If you KO an immunoglobulin adhesion molecule where will the RGC innervate?
all layers at random
What do olfactory receptors influence?
the targeting of sensory axons to discrete glomeruli in the olfactory bulb
How many receptors do the olfactory sesnory neurons express?
one and only one
What are the receptors in olfatcory sensory neurons?
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
Where do all of the same type of olfactory neuron project to?
the same glomerulus in the olfatcory bulb
What is the glomerulus?
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
Where are olfactory sensory neurons found that express the same receptor?
distributed sparsely throguhout the nose and project to glomeruli in the olfatcoyr bulb
What happens in a mouse mutant in which an odorant receptor gene is deleted?
-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
What happens if you knockout all olfactory receptor genes in an olfatciry sensory neuron?
it will still find a unique glomeruli which means there are other guidance cues involved
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?
-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
How come when in odrant receptor gene is repleced by another in a set of olfatciry sensory neurons their axons porject to new glomerulus?
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
What are the two main jobs of olfactory sensory neurons?
- determine a neurons responsiveness to specific odorants
- also help the axon to form appropriate synapses on target neurons
What have recognition molecules been found to do in the interactions of olfactory axons?
found to regulate the interactions of olfactory axons with each other and with their targets
What three decisions are need in synaptic targeting and specificity?
- decision on what general tissue and brain region the synapse is going to be made - axon guidance
- decision about what specific cell or target to make a synapse with within this region
- final decision what subcellular region of the spcific target on which you want to make a synapse
Where are different synaptic inputs directed to?
discrete domains of the postsynaptic cell
Where doe synapses form on neurons in the cerebellum?
on spatially distinct subdomains of purkinje neurons
In the cerebellum where to climbing fibers terminate?
on distinct regions of distal dendrites
In the cerebellum where do inhibitory basket cells synapse onto?
the axon initial segment which allows for a more powerful toning down of hyperexcitabulity and allows for more direct inhibition
What do inhibitory basket cells recognixze on the axon intial segment and what is it anchored by?
-IG domain proteins known as neurofascin and it is anchored by the cytoskeleton protein akyrin g
-instructs synpases to form at this region
What happens in the cerebellum to the inhibtory basket cells if you express neurofascin in other subcellular areas?
the basket cell axons fail to restruct their synapse formation to the axon intial segment
What is the role of neuronal activity if any in synapse targeting and stabilization?
activity refines synapses
Is neural activity needed for basic wiring in the synaptic connections in the retina? But what does it do instead?
-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
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?
-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
What does abolishing electrucal activitry in retinal ganglion cells cause?
decreases the remodeling of dendritic and axonal arbors
What controls the intial specifity of synaptic connections and what controles the sharpening of that specificity?
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
What is revealed at the NMJ?
the principles of synaptic differentiation
What are the three types of cells at NMJ?
Motor neuron
muscle fiber
schwann cell or glia
What are the characteristic metabolic molecular and electrical properties that identify muscle fibers?
slow or fast types
Staining of what proteins shows different MNs innervating same type of muscle?
staining of myosin ATPase
How many motor neurons innervate a muscle fiber?
one
What is slow twicth muscle for?
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
What is fast twitch muscle for?
sprinitng robust movemnt so fatigue fast and have phasic activity - 10APs/s -high frequency bursts
What is different in MNs that connect with fast and slow twicth muslce fibers?
exhibit different patterns of electrical actviity
How does the pattern of MN activity change the biochemical and functional properties of muscle?
-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
How does the pattern of electrical stimulation alone define functional properties of muscle?
-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
What does the muscle dictate for the MN?
the MNs whcih survive and the neurotransmitter phenotype
How does the MN dictate the patten of the muscle?
can define biochemical and electriphysiological proteries of muscle like FT and ST
What is reciprocal synaptic dialogue?
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
