LTP vs LTD Flashcards

1
Q

Bliss and Lomo (1973)

A

demonstrated LTP in dentate gyrus of anaesthetised rabbit - patterned neural activity changes the weight efficacy of the connection between two neurons.

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2
Q

3 experiments for calcium elevation

A

Collingridge (1984) Nowak (1984) Malenka (1988)

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3
Q

Collingridge (1984)

A

APV had no effect on EPSP generation but prevented tetanic stimulation of schaffer collateral-comissural pathway from inducing LTP

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4
Q

Nowak (1984)

A

Patch clamp techniques and varying extracellular Mg2+ . Channel only voltage independent in Mg2+ free solutions.

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5
Q

Malenka (1988)

A

Photolabile nitr5 calcium uncaging mechanism used to demonstrate that calcium elevation is both necessary and sufficient for LTP.

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6
Q

What is co-operativity?

A

Depolarisations from multiple neighbouring subthreshold presynaptic inputs can spatially summate to produce suprathreshold depolarisaion triggering LTP

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7
Q

What is associativity?

A

Stronger inputs can potentiate weaker inputs

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8
Q

What is input specificity?

A

Localised calcium influxes are generated which will only affect the affected synapses

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9
Q

Malinow (1989)

A

LTP requires transient activation of CamKII - establish LTP then apply inhibitor, makes no difference to induction to LTP

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10
Q

Shi (1999)

A

AMPA receptor subunit GluR1, tagged with GFP. 2-photon laser scanning microscopy showed most of the GluR1-GFP was intracellular, tetanic stimulation induced rapid delivery of tagged receptors into dendritic spines.

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11
Q

Sudhof and Malenka (2017)

A

-Blocking postsynaptic expression of Syt1/7 but not either alone abolished LTP in hippocampal slices. -LTP restored with WT Syt7 expression, but not expression of calcium binding deficient mutant. -Syt1/7 act as calcium sensors for calcium dependent exocytosis of AMPA in LTP - simple mechanism for AMPA recruitment. -CAMKii may phosphorylate or stably capture

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12
Q

Padamsey (2017)

A

bpAPs trigger calcium release from lysosomes - calcium reduced when osmotically ablated lysosomes. Calcium signalling mediates fusion with plasma membrane, releasing active protease cathepsin B, stimulating MMP9. MMP9 required to maintain long-lasting spine growth during synaptic plasticity.

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13
Q

What is the synaptic tagging and capture hypothesis?

A

Strong tetanisation of one synaptic pathway leads to two dissociable events - local tag setting and synthesis of diffusible plasticity-related proteins (PrPs)

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14
Q

Martin (1997)

A

Cultured a single bifurcated Aplysia neuron, making synapses with 2 spatially separated motor neurons. Perfuse 5HT onto one branch, show single axonal branch undergoes facilitation. Depends on CREB mediated transcription.

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15
Q

Emptage (2003)

A

demonstrated pre-synaptic component of LTP by visualising postsynaptic calcium through calcium sensitive dyes and confocal microscopy. Following LTP, increase in probability of single stimulus evoking a postsynaptic calcium response

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16
Q

Arancio (1996)

A

LTP induction blocked by extracellular NO scavengers, intracellular NO scavengers and NOS inhibitors to post-synaptic. Photolytic release of NO could generate LTP when paired with presynaptic stimulation.

17
Q

Gerdeman (2002)

A

LTD in striatum dependent on activation of the CB1 cannabinoid receptor - KO animals unable to perform LTD in affected areas.

18
Q

Bear and Dudek (1992)

A

Low frequency stimulation of schaffer collaterals could induce depression in EPPs in CA1 neurons. Effect prevented by NMDAR antagonists - 1Hz stimulation 99x - not physiological?

19
Q

Malenka (1992)

A

BAPTA calcium chelator prevents LTD - therefore sliding threshold model for LTP and LTD.

20
Q

Lee (2003)

A

Mice with knockin mutations in the GluR1 phosphorylation site show defecits in LTP and LTD.

21
Q

Wang (2000)

A

Expression of cerebellar LTD requires postsynaptic clathrin mediated endocytosis, as postsynaptically applied dynamin could block LTD in cultured purkinje neurons.

22
Q

Ito (1982)

A

Demonstrated through in vivo recording of purkinje cells that conjunctive stimulation of the climbing fibres and the mossy fibres in decerebrate rabbit depressed the excitation of the purkinje cells to mossy fibre stimulation.

23
Q

De Zeeuw (2011)

A

3 mutant mice targeting expression of PF-PC LTD by blocking internalisation of AMPA receptors. Used several cerebellar co-ordination tasks including adaptation of the VOR to show no motor learning impairment in mice lacking LTD

24
Q

Markram (1997)

A

Patching onto pre and post synaptic layer V cell, using current clamp to record voltage changes in the cells. Pre-post caused potentiation, whereas post/pre = depression. Increase temporal gap from 10- 100ms effect is removed.

25
Q

Magee (1997)

A

Dendritic patch recordings with calcium imaging to observe that subthreshold EPSP causes a 2% rise in calcium, unpaired postsynaptic AP caused 5%. 2 paired together, supralinear 10%. Occurred more in proximal than distal regions.

26
Q

How does bpAP enable STDP? LTP

A
  • unblocks NMDA receptors, allowing calcium influx. -BAP could be boosted by EPSP inactivation of A-type K+ channels, increasing BAP amplitude.
27
Q

How could bpAP enable STDP? LTD

A
  • Activate VGCCs that are then inactivated, reducing the calcium influx. -Calcium influx could also inactivate NMDARs.
28
Q

Sjostrom (2006)

A

Quadruple simultaenous patch recordings. Estimated distance of synapse to soma before inducing pairing protocols. Proximal synapses exhibit LTP whilst distal synapses exhibit LTD -> Adding extra depolarisation to more distal synapses could recover LTD to LTP.

29
Q

Two plasticity mechanisms part of a multifactor plasticity algorithm composed of - (4)

A

-firing rate -spike timing -dendritic depolarisation -synaptic cooperativity.

30
Q

Silva (1992)

A

First genetic knockout mouse. Alpha CamKII knockout deficient in LTP

31
Q

Malinow and Makino (2009)

A

Recombinant surface fluorescent receptors in rat hippocampal slices used to show majority of AMPARs incorporated into synapses during LTP through lateral diffusion.

32
Q

Bonhoeffer (1999)

A

local superfusion technique + 2 photon imaging show long lasting functional enhancement of synapses in CA1 produced structural changes in spines.

33
Q

Zakharenko (2001)

A

FM1-43 dye used to image changes in presynaptic function during LTP at CA3-1 synapses. Enhanced presynaptic function during chemically and electrically induced LTP.

34
Q

Zakharenko (2002)

A

mGluR dependent LTD at CA3-CA1 synapses in acute hippocampal slices has presynaptic element shown through FM 1-43 destaining

35
Q

BCM graph

A
36
Q

Lisman Graph

A
37
Q

LTD and LTP molecular biology schematic

A