Plasticity Flashcards
(93 cards)
1
Q
What is synaptic plasticity?
A
- a change in connection strength between a neuron and its target cell
2
Q
What can synaptic plasticity lead to?
A
- changes in behaviour or changes in the response to sensory stimuli
3
Q
What is sensitization?
A
- behavioural term describing an increased response to a stimulus
- does not define a form of cellular change
4
Q
A term describing a change in behaviour or response to a stimulus is not equal to?
A
- a mechanistic explanation for a cellular change
5
Q
What happens when a repetitive stimulus is applied to a motor axon of a frog neuromuscular junction that is treated with curare?
A
- a series of action potentials occurs
- curare blocks ACh which is quick to fill vesicles
- initially APs get bigger (due to p)
- Aps get smaller (n decreases as vesicles are used)
6
Q
What happens when a repetitive stimulus is applied to a crayfish neuromuscular junction?
A
- low probability of release and naturally small epsp
- continually increases
7
Q
What is synaptic facilitation (paired-pulse facilitation)?
A
- rapid increase in synaptic strength that occurs when two or more action potentials invade the presynaptic terminal within ms of eachother
8
Q
What happens when a pair of presynaptic action potentials elicits two epsps?
A
- the second ap has a greater amplitude
- facilitation
- due to an increase in p
9
Q
What happens to facilitation when pairs of presynaptic aps are separated by varied time intervals?
A
- facilitation decreases in a decay timecourse
- facilitation phase 1
- simplest forms of “memory” encoding
10
Q
What does the decrease in variance/mean and increase in mean indicate?
A
- increased amplitude is compatible with an increased P
11
Q
What is synaptic depression?
A
- nt release declines with sustained synaptic activity
12
Q
At normal physiological levels, what happens when a squid axon is stimulated with high-frequency tetanus?
A
causes a depression of epsps
13
Q
When the external calcium is lowered and the squid axon is stimulated with a high-frequency tetanus, what is observed?
A
- intermediate levels: reduces nt release, mixture of depression and augmentation
- low levels: eliminates depression, leaving only augmentation
14
Q
What does the change in depression with the change in calcium say about the mechanism of depression?
A
- it depends on the amount of nt released
15
Q
What is post tetanic potentiation?
A
- when a train of high frequency stimuli is followed by enhancement lasting several minutes
- because calcium has accumulated
16
Q
What is the difference between augmentation and potentiation?
A
- both enhance the ability of incoming calcium to trigger fusion of synaptic vesicles (mechanisms not understood)
- augmentation rises and falls over a few seconds
- potentiation acts over a time scale of tens of seconds to minute
17
Q
What are the four different forms of plasticity? How long do each of them last?
A
- facilitation (< 1 s) - 2 APs
- augmentation (5-10 s)
- post-tetanic potentiation (10s-mins)
- depression (5-7 s)
18
Q
Multiple activity dependent effects on transmitter release are overlaid at all synapses, the outcome depends on?
A
- duration of activity
- time-course
- relative magnitude of different forms of plasticity
19
Q
What is habituation?
A
- a process that causes the animal to become less responsive to repeated occurrences of a stimulus
20
Q
What is sensitization?
A
- a process that allows an animal to generalize an aversive response to non-noxious stimulus
21
Q
Touching the siphon of an Alplysia causes what process?
A
- habituation
- less gill withdrawal
22
Q
After touching the siphon of an Alplysia to evoke habituation, what happens when the tail is shocked and the siphon is touched?
A
- dishabituation/short-term sensitization (sensitization would be if not habituated first)
- more gill withdrawal
23
Q
How long does short-term sensitization last?
A
~2 hours before becoming habituated again
24
Q
What occurs if tail shocks and siphon touching are repeated multiple times?
A
- causes prolonged sensitization
- lasts for days or weeks
- simple long-term memory
25
What is the synaptic mechanism underlying short-term sensitization?
- sensory neuron for siphon excites interneuron and motor neuron that excites gill
- the tail sensory neuron excites a modulatory neuron that excites the presynaptic terminals of the siphon sensory neuron
- this increases the excitation on the gill
26
Where does 'habituation' occur on the cellular level in the Aplysia example?
- sensory neurons of the siphon are still as stimulated so there must be a depression in the sensory neuron-motor neuron synapse
- stimulating the tail sensory neuron and modulatory neuron enhances the release of nt at this synapse
27
What is short-term sensitization due to?
- recruitment of additional circuit elements (modulatory interneurons) that strengthen transmission during this period of time
28
What is the potential cellular mechanism responsible for short-term sensitization?
1. modulatory interneurons release serotonin which bind GPCRs on presynaptic terminals of siphon sensory neurons
2. stimulates production of cAMP
3. cAMP binds regulatory subunits of protein kinase A
4. liberate catalytic subunits of PKA that phosphorylate several proteins including K+ channels
5. reduces the probability of opening of K+ channels (prolongs ap and opens more calcium channels)
6. increase in calcium increases nt release of glutamate
29
What is short-term facilitation caused by?
- post-translational changes (phosphorylation) of protein (K channels)
30
What does phosphorylation of a particular kind of K channel result in?
- reduces the repolarization rate of APs (broadens AP) which increases calcium influx and nt release
31
What is R?
n*p
32
How is p affected by increasing calcium concentration?
- p is increased indirectly
33
How is p affected when the intrinsic probability of vesicle release is also enhanced?
- vesicle release machinery becomes more sensitive to calcium
- p is increased directly
34
What does long-term sensitization require?
- changes in gene expression
35
What are the steps in long-term sensitization?
- similar mechanism to short-term
1. serotonin activated PKA phosphorylates (activates) CREB
2. CREB binds to cAMP response elements (CREs) in regulatory regions of nuclear DNA, increases rate of transcription of ubiquitin hydrolase
36
What is specifically changed with the increased rate of transcription as a result of CREB binding CREs?
- stimulates synthesis of ubiquitin hydrolase
| - stimulates transcriptional activator protein C/EBP
37
What does ubiquitin hydrolase do?
- stimulates degradation of the regulatory subunit PKA
| - long-lasting increase in free catalytic subunit of PKA
38
What does C/EBP do?
- stimulates transcription of other genes
- results in addition of synaptic terminals
- long-term increase in number of synapses
39
What is the difference in mechanism of short-term and long-term effects?
- short: posttranslational modification of existing proteins
| - lon: changes in gene expression, protein synthesis, growth of new synapses
40
What provides evidence that protein synthesis is needed for long-term sensitization?
- if protein synthesis is inhibited, there is no transition to long-term memory
41
What two memory affecting mutations were discovered in fruit flies?
- dunce: mutates phosphodiesterase that degrades cAMP
- rutabaga: mutates adenylyl cyclase that converts ATP to cAMP
- amnesiac: mutates peptide transmitter that stimulates adenylyl cyclase
42
What is coincidence detection?
- two events that occur close together in time cause persistent change in behavioural responses at later times
43
How does temporal conjunction of neural activity lead to changes in synaptic strength?
- classical conditioning
44
What are the US, UR, CS, of aplysia classical conditioning?
- US: shock tail
- UR: withdraw siphon
- CS: touch siphon
- CR: withdraw siphon
45
What does "paired" mean in classical conditioning?
- to stimulate at the same time (US and CS)
46
What are the three types of conditioning that differ in time of delivery?
1. Trace conditioning: US after CS
2. Delay conditioning: US at end of CS
3. Backwards conditioning: US before CS
47
How is the classical conditioning of gill withdrawal in aplysia different from the sensitization response?
- requires fewer repetitions to produce a big withdrawal
| - showed "specificity" for siphon touch
48
What is occurring on the cellular level during classical conditioning?
- CS: influx calcium, activation of calmodulin
- US: release of serotonin
- calcium activated calmodulin mediated potentiation of adenylate cyclase (site of convergence)
49
The neuronal encoding of "coincidence" is?
- between the activity of facilitator neuron (serotonin release) and sensory neuron (calcium influx)
50
When you stimulate with the US before the CS no change in the CR is seen, this means that?
- the sequence of neural activity matters
51
On a cellular level, what explains that the sequence of stimulus is important in classical conditioning?
- adenylyl cyclase produces more cAMP
- in this state for a few seconds
- if g-protein activated, even more cAMP is produced
- calcium must come before serotonin is released to prime
52
What is the signal that temporally links activity of different neurons?
calcium
53
Why is classical conditioning an example of plasticity but not hebbian style plasticity?
- because post synaptic terminal does not take part
54
What does US then CS result in?
- a bit of sensitization but not conditioning
55
How are the temporal constraints of conditioning dependent on temporal properties of cellular processes?
- CS before US
| - calcium influx before serotonin release
56
Do you see how classical conditioning of this sort can show "specificity" for the "conditioned" stimulus?
- yes, if mantle paired with shock specificity for mantle
| - due to the timing
57
Is this (classical conditioning) consistent with the Hebbian idea for plasticity?
- No, hebbian plasticity entails correlation between pre and postsynaptic activity which produces long-term enhancement of connection
58
Where in the brain has hebbian plasticity been studied?
- hippocampus
| - CA3 to CA1 synapses
59
What is long-term potentiation (LTP)?
- patterns of synaptic activity that produce a long-lasting increase in synaptic strength
60
What is long-term depression (LTD)?
- patterns of activity that produce a long-lasting decrease in synaptic strength
61
What are schaffer collaterals?
the axons of pyramidal cells in the CA3 region that synapse on CA1 pyramidal cells
62
What results when tetanus is applied to synaptic pathway 1 and not synaptic pathway 2?
- when stimulating pathway 1, the EPSP is increased for a single stimulus
- despite coming from the same region and innervating on the same pyramidal cell, pathway 2 is unaffected
63
How long can high-frequency stimulation result in LTP for?
- for more than a year
64
Pairing presynaptic activity with ___ can cause LTP.
- postsynaptic activity
65
What does strong stimulation on pathway 1 and weak stimulation on pathway 2 result in (fig 8.9)?
- synapses strengthen for both pathways (LTP)
66
What are NMDA receptors?
- voltage dependent glutamate receptors
67
What are the main features of NMDA receptors?
- significant calcium contribution to their current
- glycine (required modulator)
- Mg2+ (voltage dependent "blocker")
68
What happens to an NMDA receptor when Mg2+ is present and glutamate binds?
- hyperpolarization because Mg2+ is blocking
69
What happens to an NMDA receptor when Mg2+ is removed and glutamate binds?
- depolarization because no Mg2+ is blocking
70
What is required to induce LTP at CA3-CA1 synapses?
- NMDA-R activation
| - NMDA-R is voltage dependent
71
What does the voltage dependence of NMDA-R explain about the process of LTP?
- NMDA-R are on the postsynaptic neuron
- in order to function (allow calcium influx) Mg2+ needs to be removed by sufficient function
- explains why stimulation of pre and post result in LTP
72
What signaling mechanisms underlie LTP?
1. Glutamate released and binds AMPA and NMDA receptors
2. AMPA receptors allow influx of sodium
3. depolarization expels Mg2+ from NMDA receptor and allows calcium influx
4. calcium activates calmodulin kinase II and protein kinase C
5. substrate phosphorylation
6. additional AMPA receptors inserted
73
What does LTP cause?
an increase in the glutamate response of a dendritic spine due to an increase in the number of AMPA receptors
74
What is the time course of glutamate sensitivity of dendritic spines during LTP?
- for more than 60 minutes
75
What can block LTP?
- "fast" calcium chelators
76
Back propagating action potentials will raise calcium concentration so why don't they enhance all the synapses on the dendrite?
- depolarization of post synaptic terminal will cause NMDA receptor to lose Mg2+
- because no presynaptic depolarization, no glutamate, no calcium influx
77
What does LTP mimic?
- the conditions of a strong tetanizing stimulus
78
What occurs before and after inducing LTP at a hippocampus silent synapse?
- before there are no excitatory post synaptic currents (EPSCs)
- after LTP there are mediated by AMPA receptors
79
Why are "silent synapses" given that name?
- because they are "silent" until the post-synaptic terminal is depolarized to activate NMDA receptors
80
What experiment provides evidence for silent synapses?
- when held at -65 mV and stimulated, the synapse is not activated
- when the post-synaptic cell is depolarized, there is a response
81
Which receptors are not present before development?
- AMPA receptors not as present before development
| - juvenile hippocampus contains many NMDA receptors but not AMPA
82
What is the difference between a silent synapse and a functional synapse?
- silent: NMDA-R only
| - functional: AMPA-R and NMDA-R
83
What is needed to maintain LTP and how was this proven?
- protein synthesis is needed
| - if a protein synthesis inhibitor is added, LTP declines in a few hours
84
What is an alternative to "new" spines?
- change in morphology of existing spines
| - expansion of or duplication of active zones and postsynaptic receptor clusters
85
Plasticity at aplysia synapses and LTP in mammalian hippocampus show?
- the same features of an early transient phase that relies on protein kinases to produce posttranslational changes in existing proteins and long lasting phases that require gene expression
86
Changes in gene expression for both plasticity at aplysia synapses and LTP in mammalian hippocampus is mediated by?
- CREB (and others)
87
Both LTP and LTD at CA3-CA1 require?
-NMDA-R
88
What leads to LTP?
- large fast NMDA mediated Ca increases trigger LTP
| - initial induction requires protein phosphorylation leading to AMPA-R insertion
89
What leads to LTD?
- small and slow rises in NMDA calcium lead to LTD
| - initial induction requires calcium-dependent phosphatases leading to a loss of AMPA-R
90
What do we mean by long-term plasticity needs to be dual direction?
- LTD can reduce synaptic strength and can "erase" LTP
| - LTP can "erase" LTD
91
What is the mechanism of LTD?
- weaker activation of NMDA-R leads to lower calcium concentration
- phosphatases are activated by lower levels of calcium which dephosphorylate substrates (internalize AMPA-R)
92
What stimuli enhances and what stimuli depresses?
- pairing enhances (Pre then post = LTP)
- anitpairing depresses (Post then pre = LTD)
- stimuli must be within 40 ms to have effect (either LTD or LTP)
93
How does the cerebellum differ in LTP and LTD mechanisms?
- high calcium concentration in spine leads t removal of AMPA receptors
