Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
45 Cards in this Set
- Front
- Back
|
volatility increases with... (5) depending on the change you can predict how long the memory will last Are these reversible? |
- changed in phosohorylation state (reversed by phosphatases ) - insertion and removal of membrane proteins (reversible but may require energy) - persistent activation of protein kinases (reversibility depends on mechanism) - production of new proteins (requires constant energy) - morphological changes at pre-existing synapses, like build new synapse or bigger one
|
|
|
What are the thoughts about molecular memory traces? |
- distinct traces may represent different memories in the same neuron - distinct traces may represent different memories in distinct neurons - different experiences may use distinct memory traces - one experience may form multiple traces in the same neutron (parallel memory traces) |
|
|
non associative memories; two examples |
- no specific association between conditioned and unconditioned stimulus- stimulus alone is strong enough to change behaviour - habituation is the decrease in a defensive reflex due to repetitive non-noxious stimulation.- conditioned stimulus alone - Sensitization is the increase in a defensive reflex due to a noxious stimulus. in unconditioned stimulus alone. you leave a scary movie and someone touches you and you jump. someone didn’t need to be touching you during the film bc you are sensitized to the stimuli. |
|
|
Why should we use the Aplysia (big slugs) system to look at memory? (4) |
- simple behaviours and neuronal circuits= reductonist methods -neurons are large and identifiable - allows for tracing of circuit - primary cultures of neurons can recapitulate the changes observed during behaviour |
|
|
Describe the gill and siphon withdrawal reflex in the Aplysia. What is sensitization and habituation in this context? |
-tactile or electrical stimulation of the siphon causes withdrawal of gill and siphon - this is an unconditioned response and is controlled by the abdomen ganglion
What is memory in this context? - for sensitization you give a noxious stimulus to head or tail and will see an increase in the time and extent of gill withdrawal to touch to the siphon - habituation- give repetitive touches to the siphon which will cause a decrease in gill withdrawal |
|
|
where could the memory “lie”? (4) |
- changes in mechanotransduction of sensory system - changes in properties of the sensory neuron - changes in circuit between sensory neutron and motor neuron - changes in the muscle |
|
|
What are EPSP and IPSPs? how are they measured? |
action potentials cause presynaptic cell to release neurotransmitter that acts as a ligand to open channels to the postsynaptic cell. this allows for ions, for an EPSP (excitatory Postsynaptic potential) this is mainly sodium and for IPSP (inhibitory PSP) this is chloride, to flow into post synaptic cell - they are measured as a change in voltage in the post synaptic cell
|
|
|
Do habituation and sensitization change the synaptic strength between the sensory neurons and motor neurons in the gill withdrawal reflex? What neurotransmitter mediated sensitization effects? |
YES experiment- fire the sensory neutron and look at the EPSP in the motor neurone. If you continually fire the sensory neutron, the sensory neutron no longer fires the motor neuron= habituation if you “shock” the neutron, the synapse will show an increase in strength, so the same stim. in sensory neutron will cause a greater response in motor = sensitization they found that is was serotonin that causes these effects application of 5ht mimicked socking the nerve and caused increase in the synaptic synaptic strength between sensory and motor neurons - removing 5ht containing neurons will a toxin reduced sensitiation - 5ht neurons fire during sensitization training and 5ht is released during sensitization
|
|
|
what are the links between behaviour vs cellular properties? |
- behavioural habituation- repeated touches leads to decrease of withdrawl - cellular depression- repeated firing of sensory neurons leads to less release ad decrease of EPSE to motor neuron - behavioural sensitization— shocking tail or head leads to increase of withdrawl - cellular facilitation- shocking nerve or in addition of 5ht leads to more release of EPSP to motor neurone |
|
|
How can we increase synaptic strength (3) ? |
- releasing more transmitter/AP - increasing the effect of releasing the same amount of transmitter by having a bigger post-synaptic response - having more synapses |
|
|
What is the equation for synaptic strength? how can we control P (3) ? |
M= NPQ M= synaptic strength N= number of synapses P= probability of release after action potential (0-1) Q= amplitude of EPSP resulting for the release of one vesicle.
How to control P - modulating calcium channels can change the amount of calcium entering with an action potential- release goes as the 4th or 5th power of calcium concentration so small changes in Ca+ cause large changes in release - the number of vesicles that are ready to release- combining of vescicles of activity zone, and priming of vescicles - coupling of calcium entry to fusion of vesicle |
|
|
what is a miniature EPSP? what may they be a proxy for ? changes in mini EPSP amplitude= what? |
- in absence of an AP, synaptic vesicles will still fuse at a slow spontaneous rate. this release of a single vesicle is called mini EPSP - they may be a good probe for changes in number of releasable vesicles, changes in P and Q - the more that occur, the more vesicles - changes in amplitude in mini EPSP indicate a change in Q |
|
|
Depression is caused by... |
- decrease in P - since there is no change in mini amplitude (same size) or mini frequency during habituation- the lack of a change in amplitude rules out a post-synaptic change so it must be PRE-SYNAPTIC - probably due to calcium- secretion coupling- either less calcium coming in during action potential or the calcium does not cause release of synaptic vesicle
So in depression: calcium comes in but it doesnt cause release :problems in calcium secretion-coupling
|
|
|
depression does not require.... |
very high frequencies; somehow the system is set up for easy depression ***habituation depends on this distinct property |
|
|
Short-term facilitation depends on... how does this work? |
PKA = a cAMP-dependent protein kinase (a kinase is a protein that acts by modifying other molecules by adding a phosphate group) 1) 5ht acts through a G-protein linked receptor to increase levels of cAMP which activates PKA 2) PKA phosphorylates the K+ channel and inactivates it making the cell more depolarized 3) this slows the repolarization of AP by making depolarizing phase longer THIS IS CALLED SPIKE BROADENING 4) this broadened AP allows increased calcium influx since channels are open longer and this leads to more transmitter release/AP 5) this leads to increased EPSP between sensory and motor neuron= more behaviour (more withdrawal of gill)
|
|
|
What is a ST memory trace? How long would it last? |
- the PKA phosphorylation of the K+ channel would be the trace - the memory would last as long as that site remains phosphorylated - short-term sensitization/facilitation lasts about 20-30 min |
|
|
Why is spike broadening not the whole story behind short-term facilitation? |
- artificially broadening the AP the same amount as 5HT does increases the EPSP but not as much as 5HT - preventing AP broadening reduces but does not remove the increase in EPSP after 5HT addition - thus, 5HT can increase vesicle release by modifying priming or docking or coupling to calcium as well as AP broadening |
|
|
Other than spike broadening, what can cause facilitation? |
- increase in priming of vesicles! - there is an increase in frequency of minis during facilitation (no effect on amplitude) bc of priming - priming is mediated by PKC (also important for reversal of depression by increasing calcium-secretion coupling) and PKA |
|
|
not everything is synaptic... How else can we increase excitability |
- increased behaviour is also do to increased excitability of the neuron not just priming and broadening - inhibiting K+ channels depolarizes sensory neuron so it needs less stim to fire and leads to less resistance to firing repeated AP so that the same stim leads to more AP - more sensory neurons fire and thus EPSPs in motor neuron are larger, leading to more behaviour |
|
|
What are the two meanings of consolidation?; What are the different molecular traces for each memory phase? |
cellular consolidation: how changes at cellular level last for a long time Systems consolidation: how memories can move from one system to another (like for initial store to a permanent store)
STM: protein phosphorylation ITM: Translation LTM: gene expression! L-LTM: new synapses |
|
|
Describe the 4 memory phases we can observe. What is the natural process of each and can we induce each? |
- short term facilitation STF (0-30min): is due to activation of protein kinases by second messengers like cAMP that leads to transmitter release- we can get this from one burst of serotonin - intermediate facilitation ITF (30min-3hrs): is independent of gene expression and depends on persistent kinase activity and translation of pre-existing mRNAs into proteins- can get this if we give serotonin for longer period - Long-term facilitation (LTF) 3h-1day is blocked by inhibitiors of RNS transcription. This block occurs during the indiction but not expression of LTF. We can induce this with spaced out serotonin injections
- Late long term facilitation (L-LTF) (> 1day ) may require the formation and stabilization of new synapses
|
|
|
Long-term sensitization memory is correlated with .... |
- an increased number fo synapses! - there are also increased size of active zones, increased docked vesicles, increased number of synapses - however as memory persists through time, only the increased number of synapses stays and the other morphological changes go away |
|
|
Describe the brick house analogy on serial vs parallel memory formation. What might the "brick house" be? What does the model predict? |
imagine LTM is a brick hose: serial: - one makes the frame of the house (STM) puts in the plaster and walls (ITM) and then lays the bricks (LTM) -this analogy fits the term consolidate which means to become stronger Parallel:
- three little pigs- one starts building straw house (STM) a stick house (ITM) and a brick house (LTM) all at the same time. The brick house takes a while so one needs the other two houses so there is somewhere to live in between (so that memory is continuous).
The Brick house might be NEW SYNAPSES, while the changes in pre-existing synapses are the straw and stick
the strong prediction of this model is that using appropriate pharm tools, one can make LTM in the absence of STM**
|
|
|
In the 3 little pigs analogy and light bulb analogy, what might gene expression be? What are some objections to the evidence for a role in protein synthesis (gene espression) in LTM? |
- in 3 little pigs, the role for gene expression might be to produce bricks - if memory is a light, we need 2 things: a socket to connect to electricity and a light bulb. Gene expression may be the making of lightbulbs and protein synthesis the socket. You need both for LTP. yes, if you block gene expression (making of lightbulbs) you obviously will block LTM but this doesn’t tell us that is is gene expression that makes memory
1) gene expression occurs in nucleus; memories stored at synapses 2) Gene expression may be necessary but t is not instructive - how would gene expression know what synapses to change? |
|
|
What regulates gene expression? How? |
- transcription factors - Genes (DNA) are transcribed to RNA only at certain times- regulated by small DNA elements that bind to transcription factors- these transcription factors act by: - recruiting the enzymes that make RNA from DNA - altering the stricture of DNA to open it up by modifying histones : activates acetylate histones and represses de-acetylate histones |
|
|
How is gene expression related to epigenetics? |
- epigenetics in this field= more permanent changes to gene expression like methylating the DNA itself instead of just acetylating a histone -learning may lead to these long term changes as well |
|
|
What transcription factor is required for LTF? What activates and regulates it? |
CREB! cAMP response element binding protein - blocking CREB blocked LTF without blocking STF - CREB is activated by 5-HT thus if bricks/light bulbs are what is required, they are not made unless gene expression is activated - CREB is regulated by a) whether it is phosphorylated (it only recruits RNA polymerase when it is) and b) activation of CREB kinases required for transcription like CREB activator |
|
|
CREB repressor (what is it, how is it involved in transcription, what does reducing it do?) |
- an inhibitory protein, the removal of which is necessary for transcription - CREB dimerizes (combines) with this protein - CREB is regulated but the ratio of CREB repressor to CREB activator - reducing CREB repressor should shift the balance to an easier activation of CREB, but one that still requires stimulation (ie phosphor. of CREB) - in Aplysia, reducing CREB results in LTF from a stimulus that normally only lead to STF **there is some evidence that spaced out training sessions reduce levels of CREB repressor |
|
|
If you pair one application of 5HT to the Aplysia neuron with the removal of CREB repressor via an antibody, what will happen? this shows that gene expression is the ______!! |
if you pair one application of 5ht (which usually will only give you STF) with removal of the repressor via an antibody, then you get LTM. So that gene expression is the only thing needed to change STF to LTF. CREB/ gene actication is the rate limiting factor for LTF (the part which determines the rate of the reactions down the line in the process) |
|
|
Give (5) examples of CREBs role in LTM |
- overexpression of CREB inhibitor blocks long-term odour avoidance memory in flies - CREB knockouts in mice have impaired LTM for fear avoidance, water mazes, social recognition - removing CREB acutely blocks LT taste aversion and water maze consolidation - removal of CREB repressor allows long-term memories to be formed more easily = smarter mice - over expression of CREB converts a stimulus that normally doesnt lead to LTM of fear avoidance to one that does
|
|
|
Lateral amygdala (important for conditioning, esp. auditory!) neurons which express more CREB are more likely to... If we kill off these neurons specifically, using DT, what happens? |
participate in the memory! - we can detect this via Arc levels - if CREB is overexpressed in a subset of LA neurons, the CREB expressing ones are more likely to turn on Arc after behaviour - If after a week, you specifically kill these neurons, the memory is erased, suggesting that memory encoded n same neurons that gene expression is activated in! But, memories before expression of CREB are fine and if we kill off random LA neurons, this does not happen |
|
|
If you wanted to make a drug that would enhance LTM but not STM you should look at.... |
if it reactivates gene expression! |
|
|
What is a synaptic tag? |
- the decision to encode memory for long-term is not just coincident synaptic activation but also a cell-wide decision to activate gene expression - how are specific synapses modifed during learning+ memory if gene expression occurs only in nucleus??: SYNAPTIC TAGGING - Gene expression is cell-wide, but only the synapses that were activated would have tags, and these cause Plasticity related proteins to do their thing. So Only synapses with the proteins AND the tag will be strengthened. The gene expression must be “captured” by the tag |
|
|
How do we study synaptic tagging? |
- look at bifurcated neurons (have two processes coming off) - you can just apply serotonin to one of the synaptic connections and not the other- you can also just apply it to the cell body, which is what they did - usually you need both gene expression and a tag to increase synaptic strenght, but in these experiments, they just increase the proteins and get synaptic strength- If you block CREB or protein synthesis (only in the nucleus, if you do it at synapse doesnt work), you block the facilitation |
|
|
Adding 5HT to the cell body only will... Addint it to only one of the two synapses (bifurcated neuron) will... |
- induce LTF seen 24 hrs later (doesnt persist untill 72), and NOT STF - this increase in strength is seen in existing synapses, there are no morphological changes - you need the same requirements for gene expression (5X 5HT, transcription, CREB) - but shows that you dont need local protein synthesis necessarily
- If you put 5ht into only one of the synapses will give you STF, ITF, and LTF (72hrs) in the one synapse but not the other |
|
|
Facilitation caused by Cell-wide vs synapse specific stimulation (3) describe the process that happens when you inject 5ht to one synapse which results in synaptic taging |
- need activation at synapse to get morphological changes- new synapses - need activation at synapse to make persistent LTF (>24 hrs) - earlier increases with synapse specific changes
- 5ht transported to nucleus to activate gene expression - tag at synapse - signal to repress cell-wide changes at other synapses |
|
|
What happens if you add 5 X serotonin to one synapses and only 1 to the other synapse (this is not normally sufficient to cause changes)? what about if you add 5ht to cell body and 1 pulse of 5ht to one synapse? What does this suggest? |
- one sees that the synapse with only 1 application of 5ht sees an increase in strength that lasts 72 hrs and has morphological changes! - if you add 5ht to cell body and only add 1 pulse serotonin to only one synapse-you see synaptic strength increase in the one you gave one pulse to but not the other
-THUS to make the tag requires less stimulation than to actually activate gene expression |
|
|
Injecting phosphorylated CREB into cell body will cause...
|
- same result as 5X 5ht to the cell body - it will activate gene expression and result in cell strength at 24 h but not 72 hrs and no morphological changes - BUT if you give pCREB and then only pulse of 5ht to one synapse you get 72hr changes and morphorolgical changes, only in that one synapse THUS LTF is not really dependent on the increase in synaptic strength - so you dont need ITF for LTF! |
|
|
How long can you separate gene expression (injecting pCREB) and tag (5ht pulse)? What can we deduce from this? |
if you inject and then pulse the 1x5ht tag to the one synapse 4 hrs later it doesn’t work, 2hrs it does a bit, 1 hr it works, -an hour after it works, 4hrs later it doesn’t work Thus tag can be either before or after gene expression, and lasts for a few hows |
|
|
Tagging relies on ____; What are 3 examples of capture? |
PKA, you dont make the tag if you block PKA
-can target MRNA to synapse for local translation - can translate proteins in soma and then transport them to specific synapses - can target proteins to all synapses, but then only have actions at tagged synapses Capture= what the tag does, not the activation of gene expression |
|
|
What is Rapamycin? what does it inhibit? What can adding it cause? What does it not block? |
- a specific inhibitor of a protein complex called TORC1, which regulates parts of translation down stream of signal transduction ( by phosphorylating proteins which increase rate of transl.) - rapamycin doesnt block most basal translation, but can completely block activation of translation in some circumstances - if you pulse 5HT this increases translation rate through activating TORC1 and this effect is blocked by adding rapamycin. - rapamycin does NOT block the translation-dependent signal from the synapse to the nucleus that activates transcription and does NOT block the tag required for synapse-specific facilitation at 24 hrs, nor the initial formation of new synapses. It is not totally understood why, or if maybe local translation at synapse is needed to produce tag -You will get morophological changes, but they arent maintained, and the synapse-specific facilitation will not be maintained |
|
|
What is local translation (at the synapse) required for? (3) The generation of new synapses requires certain traces that dont themselves lead to synaptic strengthening, what are they? (4) |
- required to send signal to nucleus - required for long-term maintenance of synaptic strength - ambiguous as to whether local translation is required to make a tag
- new growth, synaptic tag, nascent synapse formation, local translation of mRNAs at synapse |
|
|
Describe the Frey & Morris study |
-post-syaptic cell is being recorded and is getting stimulated by two pre-synaptic inputs. - when you just activate one neruon (call it S1) you get LTP in that synapse but not the other (S2) - if you keep activating constantly S1 you get L-LTP (3hrs). Giving a protein synthesis inhibitor (rapamycin) while doing this activation will BLOCK LTP - if you induce LLTP in S1 and give a protein synthesis inhibitor to S2, and then within 3 hours you activate constantly S2 you WILL induce LLTP even with the inhibitor! - WHY? because apparently stimulating the S1 to induce LLTP caused a tag to already be there in S2, so doesnt matter if you block protein synthesis |
|
|
look at this pretty picture |
|
|
|
how can tagging be seen behaviourally? (novel exposure) |
- induce gene expression with novel field experience: you give a weak fear stimulus (shock) to generate STM. they will remember the room they were shocked in for a couple hours but not like a day. Put animal in big field that is new before or after training. This causes gene expression and can promote LTF.- you can turn previous / later training from a short-term learning to long term - this process requires protein synthesis at time of novel exposure |
