Synaptic plasticity Flashcards
What are some autoimmune synapse diseases?
Lambert Eaton myastenic disease, myasthenia gravis and anti NMDA-R encephalitis
What are the quantal content, and what is it dependent on?
The mean number of vesicles released pr AP = the number of release sites (N) x the probability of release (P)
What are the mean synaptic current dependent on (give the equation)?
I = NPQ
N: number of release sites
P: probability of SV release
Q: quantal size (postsynaptic response pr SV)
How are P (probability of SV release) estimated?
By varying the extracellular [Ca2+] in an experiment
What is the pool of vesicles ready for SV release called?
The readily releasable pool (RRP)
What are the definition of short-term synaptic plasticity?
Changes in synaptic strength due to rapid stimulation, which are readily reversable when stim stops (only lasts for a few minutes or less)
What types of STP are there?
Depression, facilitation, potentiation and augmentation
What is the difference augmentation and potentiation?
Both enhances the ability of incoming Ca2+ to trigger fusion of vesicles, but in different time scales:
- augmentation: within a few secs
- potentiation: within 10s of secs or mins
Describe depression vs facilitation.
Depression: depletion of RRP
Facilitation: increase release probability
Describe the meachanism of depression on the pre- vs postsynaptic side
Pre: mediated bt changes in N, e.g., depletion of RRP vesicles, slow refilling in the pool
Post: mediated by changes in Q, e.g., receptor density or receptor saturation
Describe the meachanism of potentiation on the presynaptic side
Pre: mediated bt changes in P, e.g., longer AP trains aka tonic synapses
What is the residual Ca2+ hypothesis?
Stimulation frequency must be so fast that the residual Ca2+ has not subsided, requires fast refilling of RRP and the assumption that this mechanism is Ca2+ dependent
What does augmentation, facillitation and potentiation all depend on?
Intracellular [Ca2+]
What characterizes a depressing synapse?
High release probability, RRP siza is large at rest, refilling of RRP is relatively slow, RRP size decreases upon stim
What characterizes a facilitating synapse?
Low release probability, RRP size is small at rest, refilling of RRP are Ca2+ dependent and very fast, RRP size increase upon stim
Are depression and facilitation present in the same synapses?
Yes (it seems), many synapses display transient facilitation and persistent depression
What are the roles of STP?
Depression: “low pass” filter, info about start of stim
Facilitation: “high pass” filter, info about persistence of stim
What are the molecular mechanism behind STP, and what proteins are involved?
Vesicle priming:
- Munc13:
Munc13A –> tight coupling –> depression
Munc13B –> loose coupling –> facilitation
- Synaptotagmin: facilitation sensor (syn7 has a higher Ca2+ affinity –> binds to residual Ca2+ –> facilitation)
What is the definition of LTP?
The strength of synapses between neurons in the CNS is potentiated for prolonged periods following brief but intense synaptic activation
How does spaced repitition affect short term memory?
Converting it into long term
What are habituation?
A decrease in effectiveness of a stimulus in creating a response following repeated exposure to the stimulus
What are sensitization?
An increase in sensitivity/response to a stimulus following repeated exposure a strong/painfull stimulus
What are the molecular mechanism behind LT sensitization?
PKA recruit MAPK + CREB –> gene transcription
What are the molecular mechanism behing ST sensitization?
PKA inhibits K+ channels –> stronger depol and Ca2+ influx
How does spatial training affect the hippocampus?
Gray matter increase
Where are the mechanism behind LTP, pre- or post?
Postsynaptic
What is essential for LTP?
What fires together, wires together: the activity in the pre- and post synapse needto occur at the same time
What is the difference between homo- and heterosynaptic transmission?
Homo: LTP is restricted to the input paired with the postsynaptic depol
Hetero: LTP can spread from activated synapses to nearby synapses that have not undergone the pairing procedure
What is the mechanism behind heterosynaptic potentiation, and what does it possibly play a role in?
Ca2+ diffusing via NMDA-R activation
Possible role in associative learning
What receptor activation does LTP rely on?
NMDA-R, as it is Ca2+ permeable
What are NMDA-R activation dependent on?
AMPA-R activation: depol removes Mg2+ block from NMDA-R
What is the induction of LTP due to?
Accumulation of postsynaptic Ca2+ - a brief increase (2.5s) after tetanic stim is sufficient
What are spines?
Micron-sized protrusions along the dendritic shaft, that limit the diffusion of proteins and Ca2+ ions
Describe the signaling pathway behind LTP.
Glutamate binds to and gates AMPA-R —> influx of Na+ —> depol. —> Mg2+ block in NMDA-R is removed —> NMDA-R is gated (glut. also binds here) —> influx of Na+ and Ca2+
—> Ca2+ activates CaMKII and PKC —> phosphorylation of AMPA-R
—> Ca2+ activates synaptotagmins —> insertion of new AMPA-R in the membrane
What are LTP accompanied with?
Morphological changes in the postsynaptic membrane: spines
What are the difinition of LTD?
A long lasting decrease in the efficiency of synaptic transmission mediated by the synaptic activation of AMPA-Rs
What receptors are essential for LTD?
Also NMDA-Rs, as the slow and small increase in [Ca2+] here activates phosphatases –> internalization of AMPA-Rs
How are the spike-timing dependent plasticity in LTP vs LTD?
LTP: postsynaptic AP comes after pre AP
LTD: post AP comes before pre AP
What are the role of astrocytes in synaptic plasticity?
Release D-serine which are a co-ligand of NMDA-R
What disease is thought to be a plasticity disease?
Alzheimers
What are some mutation/genetic synapse diseases?
ADHD, schizophrenia, epilepsy etc.
How are AD a plasticity disease?
Blocking axonal transport –> LTP is no longer lasting
What types of synapse diseases are there?
Protein misfolding, plasticity, autoimmune, mutations/genetic leading to disruption of either the pre- or postsynaptic machinery
How does synaptic genes differ from average genes?
They are longer, and therefore more suceptible for mutation
What are diseases caused by malfunction in the SNARE complex called? Mention one.
SNARopathies
Epilepsy
