LTP in learning and memory

Question 1

Bliss and Lomo (1973)

Answer 1

First demonstrated LTP in the dentate gyrus of an anaesthetised rabbit. Patterned neural activity changes the weight efficacy of the connection between 2 neurons.

Question 2

Collingridge (1984)

Answer 2

APV had no effect on EPSP generation, but prevented tetanic stimulation of Schaffer-collateral pathway from inducing LTP.

Question 3

Nowak (1984)

Answer 3

patch clamp techniques and varying extracellular levels of Mg2+. Channel only voltage independent in Mg2+ free solutions

Question 4

Malenka (1988)

Answer 4

Used photolabile nitr-5 Ca2+ uncaging mechanisms to demonstrate that calcium elevation is both necessary and sufficient for LTP.

Question 5

5 properties of plasticity demonsrated by NMDAR signalling

Answer 5

• rapidly induced
• long lasting
• co-operativity
• associativity
• input specificity

Question 6

What is co-operativity?

Answer 6

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

Question 7

What is associativity?

Answer 7

Stronger inputs can potentiate weaker inputs

Question 8

What is input specificity?

Answer 8

Localised calcium influxes are generated which only affect single synapses.

Question 9

Patient HM

Answer 9

Profound anterograde amnesia following bilateral removal of the anterior hippocampus to treat intractable epilepsy.

Question 10

O’Keefe (1971)

Answer 10

Electrodes in the dorsal hippocampus of rats. Plot the path of the animal and superimpose firing of single cells, realising that particular cells fire when the animal is in a particular place in a field. Identified place cells in hippocampus- as a population represent a spatial map.

Question 11

Morris (1982)

Answer 11

Used morris water maze to show that spatial learning is impaired in rats with hippocampal lesions.

Question 12

What is Morris Watermaze?

Answer 12

Rodent dropped into opaque pool and uses extramaze cues to learn where a hidden submerged step is.

Question 13

Morris (1986)

Answer 13

APV infusion, using intracerebroventricular osmotic minipumps, impaired watermaze performance.

Question 14

Critique of Morris (1986)

Answer 14

Drugs may have diffused to other brain areas, therefore secondary effects on sensorimotor ability or motivation. APV animals unable to shake themselves off when on platform, often falling back into the water.

Question 15

Tsein (1996)

Answer 15

Cre/Lox mice with CA1 specific NMDAR KO. No LTP on Schaffer collateral/CA1 synapses and impaired on standard watermaze tasks.

Question 16

Critique of Tsein (1996)

Answer 16

• Also impaired on landmark test when a flag is put on top of the platform.
• Cre expression in the cortex observed

Question 17

Bannerman (2012)

Answer 17

Highly specific hippocampal KO of GluN1 with minimal NMDAR ablation in cortex. As good at watermaze task as controls.

Question 18

Bannerman (2013)

Answer 18

Experiments showing KO mice were not impaired in acquisition of the watermaze task when had to chose between 2 visually identical beacons based on extramaze cues. Subsequently impaired on trials starting closer to the decoy beacon, conducted post-acquisition. Therefore Hippocampal NMDARs act as part of comparator system to detect and resolve conflicts where two competing behavioural response options are evoked concurrently.

Question 19

How to prove causality?

Answer 19

Implant memory by selectively potentiating synapse through NMDAR-LTP. OR - identify neurons potentiated during memory acquisition and selectively depotentiate to see if the memory is lost. Immediate early genes - Arc/Arg1.3 - promoters could drive ChR2 expression?

Question 20

Malinow (2014)

Answer 20

Mice where tone replaced with optogenetic stimulation of neural input from auditory nuclei to the lateral amygdala. Pairing this with foot shock produced CR that was sensitive to extinction and blocked by NMDAR during conditioning. Slice experiments showed AMPA/NMDAR component of synaptic response, showing LTP had occurred at optically driven inputs to lateral amygdala neurons. Then LTD protocol - inactivation of memory then could reactivate with LTP.

Question 21

Whitlock (2006)

Answer 21

Immediate avoidance protocol in mice - therefore LTP after single trial. Showed changes in transcription in hippocampus, NMDAR phosphorylation.