L7 LTP/LTD Flashcards
(15 cards)
What is hippocampus function in memory?!
- key in spatial and episodic memory, association between events and place
Relevance of CA3–>CA1 synapse?
- mechanism of LTP best understood at CA1 area
- theta bursts most effective in producing synaptic change
- more repetition, more likely change of strength will take place
- decrease in synaptic strength can also happen (LTD)
what is the mechanism of induction of CA3-CA1
- post-synaptic
- NMDA-R activation - blocked with AP5
- post-synaptic rise in intraC Ca2+, blocked with intraC injection of Ca2+ chelator EGTA
- postsynaptic depolarisation - blocked by injection of negative current to hyperpolarised membrane potential
How is it that LTP and LTD induction rely on the same process?
There is a frequency threshold
1Hz for 20 mins would be LTP
mechanism of early expression of LTP
- LTP blocked by protein kinase inhibitor
- LTP associated with increased phosphorylation of AMPA receptor GluR1 subunit at Ser831. Both PKC and CaMKII can target this site
- HFS is generating sufficient intraC Ca2+ to drive activation of protein kinases to cause phosphorylation, which modifies conductance of AMPA-R, improved current flow and EPSP amplitude
- EPSP larger as it is proportional to current flowing through channel
What is a second feature that allows post-synaptic conductance in LTP?
- mobilisation of AMPA receptors, encourages them to be inserted into post-synaptic density opposite the pre-synaptic terminal
- number of AMPA receptors increases a secondary process helping support maintenance of increase in post-synaptic sensitivity
so… more conductive and more of them
How does LTD differ from LTP?
opposite effect at CA3–>CA1 - dephosphorylation target
- LTD induction protocols lead to dephosphorylation of S845 on the GluR1 subunit of AMPA-Rs
- decreased open time probability
- initiates retrieval of AMPA-R from synaptic membrane by endocytosis
how does increase in intraC Ca2+ give rise to kinases and phosphatases?
Calmodulin affinities
- low intraC Ca2+ leads to increase in dephosphorylation of CaMKII and AMPA-Rs
- high intraC Ca2+ leads to increase in phosphorylation of CaMKII and AMPA-Rs
what determines state of macroscopic conductance of EPSC
Two phosphorylation sites on AMPA-R GluR1 subunit at Ser831 and Ser845
How does LTD/LTP differ from Aplysia mechanism
- different but basic principle is still the issue that rapid biochemical changes in synaptic function
- only way to modify synapses so they can support dynamic nature of encoding is to have rapidly switchable biomechanisms to determine that the changes have been supported
what happens during late stages of CA3–> CA1 LTP?
- starts with increase in postsynaptic Ca2+
- whole mechanism involving CREB/IEGs results in new protein synthesis and long-term synaptic changes (synaptogenesis)
- synapses exhibit Hebbian LTP and anti-Hebbian LTD
What is a quick summary of the bidrectional model of plasticity?
- 3 rapid postsynaptic changes that occur - (de)phosphorylation of AMPA-Rs, insertion/removal of AMPA-Rs, increase/decrease in no. of syanptic contacts
- followed by both pre and post-syanptic remodelling to re-enforce changes
MWM
Morris water maze:
- attempted stimulation of entire EX input to DG with HFS
- shows LTP does occlude learning?
- might need more on details in case it comes up…
Optogenetic experiment
- contextual fear conditioning with optogenetic activation of diff context engrams
- subjects freeze in ‘wrong’ context
- engram being generated isn’t just down to a noxious stimuli, just initial context
- brain then decides how to feel
What is good evidence that supports Hebbian LTP as a good model for memory formation mechanisms
They occlude one another
