I2 - key papers Flashcards
(21 cards)
what is the body of evidence for glutamate reducing Pr? [largely Padamsey]
- endogenous glut release reduces increases in Pr observed w Hebbian stimulation
- reductions not seen when glut Rs blocked
- blocking postsyn NMDARs via MK-801 does not prevent reductions in Pr when glut applied
- pre-syn NMDAR KO in CA3s prevented Pr release
describe Harnett 2012
dendritic electrical compartmentalisation
examined resistance effects between spine heads + dendritic shaft, how it affects single synapse
* used caged glutamate + dendritic patching
* long neck = more resistance, above 500 MOhms cause cause more amplification of signal and increase coactivity of other spines, increasing computation
describe Emptage 1999
dendritic Ca signalling
ca reporter dyes + single cell imaging in hippocampal slices
* stimulate synaptic input onto individual spine, measure intracell Ca increase with laser
* increase is input specific and correlated with EPSP incidence
* demonstrated single synaptic events evoke NMDAR-mediated Ca release from internal stores in dendritic spines
* imaging resolution + dye properties may have limited spatial + temporal resolution
describe Nevian & Sackmann 2006
dendritic Ca signalling
the correlation between volume-averaged Ca2+ transient in spines and direction of synaptic modifications is poor
* investigation needed by microdomains to examine role of spines in cellular mechs of STDP
who visualised AMPAR trafficking to dendritic spines during LTP?
Malino 1999
visualising AMPAR trafficking to spines during LTP
* hippocampal neurons expressing GFP-tagged GluR1 AMPAR subunits
* image distribution before and after tetanic stimulation
* rapid delivery of GluR1 to spines
* dependent on NMDAR as blocked by APV
describe Sjostrom & Hausser 2006
dendritic STDP bAps
dendritic bAPs are crucial for induction of STDP + LTP
* coincidence of bAPs with EPSPs = critical
* outcome of STDP depends on location fsynapse along the dendrite (where the dendritic spine is)
* in cortex, giving the same pre-post induction produces an LTP close to the cell body but LTD at distant synapse
describe Shi et al 1999
AMPAR insertion
tetanic stimulation induces clustering of GluR1-GFP at the base of a spine
* clusters are related in spine apparatus?
describe some of the work detailing AMPAR insertion (related to memory?)
myosin Va + Vb
translocation of AMPARs is mediated by myosin Vb
* Kennedy 2010: tagged GluA1 in transferrin-receptor +ve recycling endosomes are exocytosed to spines adjacent to PSD - glycine induced
* Wang 2008: blockade of myosin Vb w RNAi reduces LTP-induced SEP-GluA1 insertion + reduced hippocampal slice LTP
* Correia 2008: Va mediates translocation from shaft to spine. neurons w siRNA from Va -> blockade of synaptic GluA1 delivery + LTP
myosin mutants show normal plasticity, compensation by other myosins
describe Ling 2006 & Volk 2013
PKMz
Ling 2006:
* staurosporin (generic PKC inhibitor) does not block LTP, but ethylerine (PKMz inhibitor) does, and so does ZIP, developed by researchers
Volk 2013:
* however, in PKMz KO, there is still LTP, but ZIP still works, obvz could be some compensation
* PKMl proposed but no decent evidence really came out
describe Frey & Morris 1997 and how they came to the synaptic tag + capture model
came from SPM
found that if 2 LTPs induced at synapses near other other, one woud be E-LTP and one L-LTP
* if fired spatiotemporally similarly, E-LTP steals L-LTP proteins + machinery to strengthen its own synapse
* the events in spatiotemporal proximity are bound in memory, thus could represent engrams
* they are specific to the synapse, and the plasticity encodes the entire associative memory
their expt:
* 2 sets of schaffer colateral cells synapse on some population of CA1s
* when protein synthesis blocked, conversion of L-LTP stopped: mRNA is key
describe Bannerman 2012
hippocampal GluN1 KO in CA1s
* mice are just as good in the Morris water maze at learning, NMDAR not dependent on that
* but had deficit in reversal learning when platform moved
* and in spatial discrimination task, where had to distinguish between 2 black footballs, the KOs would routinely go to the wrong one first if placed there -> KOs have problems disambiguating spatial memories
* platisticity is needed for memory retrieval
describe Nabawi 2014 & Ryan 2015
forgetting due to LTP/LTD
Nabawi: optogenetically induced CS-US tone-footshock can be forgotten by LTD induction and retrieved by LTP
Ryan: using ansionmyocine (protein synthesis inhibitor) post-task can induce memory loss which can be retrieved by optogenetic reactivation of engram cells
describe experiments detailing other options for the substrate of memory
Cohen-Aramon: poly-ADP ribosylation, fast + transient decondensation of chromatin by polyADP-riobsylation enables transcription needed to form long term memories (reiterated in mice)
Biergans 2015 + Halder 2016: DNA methylation patterns are altered in bees after training and in mice after contextual learning
describe Bedecarrats’ 2018 expt
slug.
injection of RNA from trained to native aplysia successfully transfers memory of sensorimotor reflex
* DNA methylation input specificity, could arise from Arc mRNA, a marker for plasticity, localised to NMDAR sites
describe progression of expts into LTP
Bliss & Lomo 1973: repeated short high frequency stimulus increased EPSPs for a long time. followed up in rabbit DG for 16 weeks
Collingridge 1983: this is dependent on NMDAR: doesn’t occur when APV present
dependent on Ca:
* Lynch 1983: EGTA mops up post-syn Ca, no LTPs
* Malenka 1988: artificially elevate Ca2+ through photolysis, induce LTP
describe evidence for STDP from Caporale & Dan 2008
inhibitory synapses cope differently with STDP than excitatory ones
* at some GABAergic synapses it depends on L-type VGCCs as well as NMDARs
* proposed coincidence detector for tLTD: activation of mGluRs & Ca influx through VGCCs leading to PLC activation
describe Turrigiano 1999
homeostatic plasticity
- add TTX to block NA channels or GABA antagonists to increase APs
- if reduce activity, EPSPs get bigger
- if enhance activity, EPSPs get smaller
- SCALED, not generic
e.g. naturally, if Ca is high, intracell levels rise and condutances are modified to decrease activity, though it now encodes something new
seen in drosophila NMJ, if FAS2 decreased to 10% of normal levels, number of pre-syn boutons decreases but muscle activation stays the same as number of active zones increases
describe Malenka 1993 + Lee 1998 re LTD
Malenka = PP1 inhibitors block LTD induction, PP1 is not Ca sensitive but metabotropic LTD has Ca-sensitive component (could be calcineurin)
Lee = thought that since kinase does LTP, phosphatase would do LTD. found removing phosphorylation reverses LTP predisposal
describe Hey-Kuang 2003
remove the phosphatase sites from GluA1 via double KO
* no phosph sites = no LTD
describe Malinow 1989
PKC
H-7 ihibition of PKC + CamKII
* add H-7 to brain slice once LTP established
* if repeated phosphprylation is the answer to LTP, LTP should disappear
* it doesn’t
* must be PKMz, an atypical PKC which is active indefinitely
how does STDP differ at inhibitory synapses to excitatory ones?
- in inhibitory, pre -> post = LTD and psot -> pre = LTP
- can have symmetrical window (hippocampal CA1)
- or overlapping spiking -> LTD, non-overlapping -> LTP
- asymmetric window: GABergic entorhinal cprtex
