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50 Cards in this Set
- Front
- Back
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Why do you need NMDA receptors?
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need them because they are the ones who let in the calcium.
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What is CaMKII turned on by?
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turned on by Ca2+
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How is Ca2+ gobbled up?
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put in Ca2+ chelator BAPTA
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What is the outcome of a homosynaptic LTP?
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fire a lot which causes depolarization and removes the Mg2+ block which lets in Ca2+
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What is the outcome of a heterosynaptic LTP?
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fire once which releases glu, but a neighboring synapse is depolarized enough which removes Mg2+ block and lets in Ca2+
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How do you know for sure what is an AMPA receptor?
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1. specifically block the AMPA receptors
2. or block the NMDA receptors by hyperpolarizing it and then isolate the AMPA R activating |
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What happens when their is no AMPA?
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A silent synapse before LTP and after LTP, there is a greater AMPA current
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What are some LTD features?
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1. Cellular connections
2. LTD features: coincidence detection in postsynaptic Purkinje cells of joint input from parallel fibers and climbing fibers 3. Consequence: PKC activates kinase; phos-AMPA Rs internalize 4. Differences from LTP: no role for NMDA Rs; kinase rather than Ptase drives AMPA R intern |
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What is LTD?
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A long lasting reduction in PSP amplitude.
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What is the NMDA receptor role of LTD?
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mediated by NR2B-containing receptors, extrasynaptic. monitor "spillover glutamate" as opposed to NR2A-R's at synapse.--> It's as though it says that there's too much activity coming through.
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What is the physiological role of LTD?
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homeostasis
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What is the mechanism of LTD?
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calcium dependent--> activates phosphatases--> internalization of AMPA-R's.
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What is the mechanism for postsynaptic LTD in the hippocampus?
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Glutamate is released into the synaptic cleft and binds to NMDA receptors which releases Ca2+ into the postsynaptic vesicle. Then protein phosphatases dephosphorylates substrates by taking phosphates off of proteins. Then internalization of AMPA receptors.
*note the clathrin in the endocytosis |
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What is the mechanism for postsynaptic LTD in the cerebellum?
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*cerebellum is involved in fine motor control
So perkinje cells have antenna-like-dendrites which synapse with parallel fivers from granule cells. parallel and climbing fiber fire at the same time and cause a LTD. so the climbing fiber converges with activity in the parallel fibers which cause LTD (depression) *Climbing fiber might serve a modulatory role, teaching the perkinje cell what input to pay attention to. |
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What is the mechanism for LTD similar too?
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Gq because glutamate is released into the synaptic clef and binds to mGluR g protein and Na+ channels. This turns on PLC which cleaves a phospholipid into DAG and IP3 where IP3 causes Ca2+ release by opening channels and DAG turns on PKC. Increase protein phosphorylation and activate Ca2+ binding proteins.
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Why is synapse formation a challenge to the early nervous system?
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Because you need to know where and what kind of synapse to make; and you need that same machinery throughout adult life for the purpose of synaptic plasticity.
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What are the two extremes of synaptic structural complexity?
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1. Vertebrate NMJ
2. Glutamatergic spine synapses in the CNS: tiny compared to the NMJ; but you have an enormous number of these types of synapses. |
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What is in between the presyn. and post syn. terminals of the NMJ and what does it house?
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They are called regulatory molecules which house the enzyme AChE, when the ACh is released must be chewed up quickly or the receptors will desensitize
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What do the dentriditic spine act as?
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They act as a way to compartmentalize things
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What are the morphological features of NMJ development?
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1. Initial contacts
2. Multiple synapses 3. Monosynaptic-mediated by competition -->The synapses compete against each other so that one wins and the other recedes. If you block the competition, you'd keep all the synapses and would remain in embryonic state. 4. Maturation--> infolding, basal lamina, schwann cells (glia that wrap around, keep the NT in, make the signaling molecules work) |
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True or false. Denervation produces increase nAChRs extrajunctional like in embryonic muscle.
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True. If you take away the nerve, then you will see more nAChR's popping up all over the place in the muscle, where there is no synapse. which is like a fetal muscle which has nAChR's randomly
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Is it a tropic factor (something secreted by the nerve that tells the muscle what to do) or electrical activity (the AP coming down the nerve and making the muscle contract) that explains the number muscle nAChR's?
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ex. was produced. Cut the nerve and let it degenerate and then innervate the muscle directly, tricking it into thinking it was staying innervated keep the same distribution of AChR's--didn't get extrajunctional receptors meaning electrical activity controls AChR distribution
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Activity reduces extrajunctional nAChR, how?
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It depresses synthesis; rapid turnover causes their loss. so ACh--> activity--> AP-->ca2+--> decrease nAChR and increase nAChR internalization (extrajunc)
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What is the result of muscle fibers being multi-nucleated and being formed by the fusion of many myocytes?
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The muscle is able to make a whole lot of nAChR's, and they're just floating around. Activity (and the ca2+ that accompanies it) says; stop making all those nAChR's, ones at the actual synapse get stabilized and those which are extrajunctional are internalized and degraded.
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True or False just because it's activity that decides the distribution of AChR's in the frog expt, that doesn't mean that trophic factors have no effect?
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True. Tropic factor are secreted by motor neurons into the synaptic cleft and they bind to Erb B receptors (TM proteins) on muscle and increase AChR synthesis (also binds to schwann cells).
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What acts as a counter command to the role of electrical activity?
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neuregulin. It sys keep making receptors where the nerve is, while the activity says stop making them elsewhere.
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what is agrin?
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protein secreted by motor neurons into the NMJ synaptic cleft. It binds to MuSK (muscle tyrosine kinase) on muscle--> activates pathway--> recruits Rapsyn to the NMJ---> clusters and stabilizes AChR's at the synapse.
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what happens when fiber is Agrin deficient?
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The fibers keep going and keep going trying to find a terminal, but can't seem to find a synapse; agrin affects what the nerve terminal will do; tell it whether it found home or not.
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What is the role of agrin and ACh in NMJ postsynaptic development?
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ACh--> activate receptors--> Ca2+ (which enters during a stimulus)--> tells nuclei to stop making so much receptor and internalize and degrade the AChR's. Agrin (acts locally because it can't diffuse)--> tells nuclei to make AChR's and stop internalizing the ones that are nearby and stop degrading.
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What are two antagonistic processes?
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Agrin doesn't need the depol like Ca2+ and so wins in the immediate vicinity of the synapse while ACh acts more broadly and wins away from the synapse because the agrin can't diffuse
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What does neuregulin (nrg) (trophic factors) do?
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helps w/ schwann cells
ACTIONS: binds to ErbB receptors on muscle; increase nAChR synthesis |
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What are two complex structures of major synaptic types on neurons?
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1. Glutamatergic (excitatory): usually on spines
2. GABAergic (inhibitory): on dendritic shafts |
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What are four developmental sequence (glut syn) of major synaptic types on neurons?
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1. Filopodium extends from dendritic shaft
2. initial contact with axon projection 3. Inductive events: specific transynaptically active component 4. molecular maturation a. presynaptic active zones appear b. postsynaptic scaffolds c. cause increased NT release and receptor responsiveness |
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What are intercellular synaptogenic factors?
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Factors that promote synapse formation between cells.
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What do cell adhesion molecules do?
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(transmembrane proteins) connect, align and position the terminals
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How do protocadherins get variety?
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Get a variety by putting together different exons in the same genes (similar to how we get the variety of antibodies in the immune system)
-many variants possible through RNA editing; specific adhesion molecules |
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What do Neuroligin (Nlg)/neurexin (Nrx) do?
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So postsynaptic Nlg (binds PSD-95) binds to presynaptic Nrx which align PSD-95 postsynaptically to
1. stabilize the synapse and align "pre" and "post" machinery * so these things aren't just glue holding two ends together; they have that cytoplasmic side tail which signals to the inside that we need the components for making a synapse. *THe interaction of neurexin w/ neuroligin is central for recruiting and retaining cytoskeletal elements that localize synaptic vesicles to the presynaptic terminal and mediate their fusion. |
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What is synCAM?
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homophilic interactions across the synapse. Acts like Nrg/Nrx bridge across the synapse, but expressed by diff cells.
*CAM= Cell Adhesion Molecules |
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What are the three recruit glutamate receptors?
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1. NARP
2. EphB2-R's/ephrins 3. stargazin (TARP) |
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what does NARP do?
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secreted proteins binds to and clusters AMPA'R's. Secreted and forms a kind of latice
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What does EphB2-R's/ephrins do?
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(postsynaptic); bind Ephrin (presyn) -->cluster NMDA-R's; increase Ca2+ flux capability
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What does stargazin (TARP) do?
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acts like an "auxiliary" subunit of AMPA-R's --> traffic to PSD-95 sites and adhere. Makes sure that the AMPA's stick where they're supposed to. The mutation in this protein resulted in a mouse that would wander around gazing up at the "stars"
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What is different of the arrival of 80nm dense-core vesicles?
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normally the SV's that release NT are clear, but we always knew that you could get these dense-core versions which are different; not made of the same membrane pieces.
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What do 80nm dense-core vesicles do?
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They do not carry NT across the membrane, but bring these proteins, building blocks that you need to tether the SV's that will be produced and which will be tethered until Ca2+ is present.
-to do this you need release sites, you need cell adhesion molecules that reach across from the postsynaptic side, where they bind to PSD-95, to the presynaptic side and say that this would be a good place for an active zone. And on the presynaptic side the neurexin and such gather together the SNARE's,etc.. that you need for the vesicle release site. |
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The presynaptic events-- arrival of 80 nm dense-core vesicles, what do they do?
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1. Deliver presynaptic "active zone" components: e.g. t-SNARES (syntaxin, SNAP) for the surface membrane (not SV components such as v-SNARES like VAMP and synaptophysin)
2. Deliver organizing/structural proteins for presyn side: bassoon, piccolo, others ("small ensemble of players...") |
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What are the adhesive factors in synapse formation?
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-Cadherins
-Protocadherins The initiation of a synapse depends centrally upon local recognition between the presumptive pre- and postsynaptic membranes mediated by members of the cadherins and protocadherins family of Ca2+ cell adhesion molecules. |
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What intercellular synaptogenic factors recruit glutamate Receptors to the synapse?
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1. NARP: secreted protein binds to and clusters AMPA receptors
2. EphB2 receptors: postsyn; activated by ephrinB (presyn); clusters NMDA receptors and enhance their calcium effects 3.Stargazin (TARPs); acts like an "auxiliary" AMPA receptor subunit; helps AMPA receptors traffic to the synapse and link to the PSD-95 scaffold there. |
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What else is neurexin important for?
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It is important for localizing voltage-gated Ca2+ channels to insure local vesicle release.
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What else is neuroligin important for?
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upon biding neurexin, is essential for localizing neurotransmitter receptors and post synaptic proteins to the postsynaptic specialization.
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What is the developmental sequence for neurons?
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1. filopodium extends from dendrite
2. Initial contact with axon terminal/branch 3. Inductive events: specific transsynaptic acting components 4. Maturation: presynaptic active zones, postsynaptic scaffolds, increased NT release and receptor responsiveness. |
