Learning, memory and synaptic plasticity Flashcards

Question

What did the study on learning in the Morris water maze with mutant mice vs. wild type mice show (Need and Giese, 2003)?

Answer 1

> Wild type mice showed improvement in learning over time > Mutant mice did not show improvement > Training curve alone does not suffice as indicative of impaired spatial learning in the mutant mice or of spatial learning in wild type mice - mice might be using alternative strategies - > memory prove trial that indicates different strategies: - learning that there's no escape - use of platform - strategy learning - spatial strategy

Answer 2

> Amount of time spent by control mice in training quadrant indicates: - clear spatial bias - evidence for spatial memory > Amount of time spent by drug treated mice in training quadrant indicates: - lack of spatial memory (random search of platform in the pool) > Drug treated mice = with AP5: NMDAR blocker -> blocking NMDA receptor impairs spatial learning > Drug was relatively high -> performance abnormalities in some animals -> blocking NMDA receptors not only blocks LTP but also blocks long term depression

Answer 3

> Mice learn that going in the dark compartment, they receive a mild electric foot shock -> learn to avoid the dark > Can be learned in a single trial > Task requires the hippocampus

Answer 4

It would jeopardise the mouse's association between the dark compartment the foot shock

Answer 5

> Useful in the study of molecular and cellular processes due to animals all learning at the same time > More suitable in the study of learning and memory processes vs. water maze where there's lack of synchronisation in animal behaviour -> more noise in analysing molecular and cellular mechanisms > Easy to distinguish short term memory (e.g. 30 min) and long term memory (24h)

Answer 6

> Wild-type animal avoids dark compartment (spends more time in lit compartment) > Mutant animal: hippocampal process is impaired in both long term (24h) and short term (30 min) memory - doesn't remember receiving the shock in the dark compartment so it's still motivated to go there

Answer 7

"When an axon of neuron A excite(s) neuron B and repeatedly [...] takes part in firing it, some growth processes or metabolic changes take place in one or both neurons so that A's efficiency as one of the cell firing B is increased."

Answer 8

It is the synaptic transmission that is enhanced not the firing, when axon of neuron A excites neuron B and repeatedly participates in firing it

Answer 9

Only a small number of synapses undergo LTP

Answer 10

> Only the synapses of trained animals show 150% EPSP slope ; never observed in naive animals - some synapses are severely potentiated: true for 30 min, 1 and 2 hours - > these synapses have produced LTP > No LTP was induced in the performance controls - no association between darkness and shock > LTP was only induced only in animals trained in the inhibitory avoidance task => behavioural training can induce LTP > LTP is NMDA receptor-dependent and occurs during memory formation

Answer 11

Whilst a limited number of drugs allow s to block particular molecules, genetics allow us to manipulate any gene of interest

Answer 12

LTP can be blocked by generating mutant mice 1. Impairment of the molecular process 2. Impairment of LTP 3. Impairment of learning and memory

Answer 13

Discovery of antibody diversity > Method of study: region-specific knockout mice - knock out an essential NMDA receptor subunit (GluN1) exclusively in the hippocampus, and study its impact > Result: - Succeeded in having a mutant mouse with an active Core recombinase exclusively in the CA1 hippocampal area - > knocking out the gene that encodes GluN1 blocks NMDA receptors

Answer 14

Knocking out NMDA receptors in the CA1 impairs spatial learning - findings consistent with pharmacological blockage of NDMA receptors resulting in blockage of spatial memory - > impaired LTP induction impairs spatial memory > However, NMDA receptors can also block long-term depression

Answer 15

CaMKII is dependent on high levels of Ca2+ -> when Ca2+ levels drop back to baseline, enzyme is inactive > However, CaMKII can phosphorylate itself at threonine-286, which is within the regulatory domain - - phosphorylation at threonine-286 = further conformational change that entraps the bound calcium calmodulin - > at baseline levels, there is still bound calcium calmodulin -> enzyme remains active > Autophosphorylation event thought to be an important event for maintaining LTP

Answer 16

> Alanine cannot be phosphorylated ; doesn’t have a hydroxyl group = block the autophosphorylation at threonine-286 -> CaM Kinase II that is normally active with a presence of calcium calmodulin => Autophosphorylation of CaMKII at threonine-286 I fundamentally important for the induction of LTP

Answer 17

Memory probe trial > Wild-type animals have a selective surge in target quadrant > Mutant animals have random surge -> no spatial memory > Mutants lack LTP induction and spatial memory -> LTP induction correlated to spatial memory formation

Answer 18

> ZIP erased the memory of animals -> erased LTP -> strong correlation between LTP and memory maintenance > ZIP: peptide that blocks protein kinase M zeta - ZIP blocks LTP maintenance mechanism, via PKMzeta > However it has bee shown that when PKMzeta is knocked out in mice, ZIP is still able to block LTP maintenance -> ZIP might also act directly on our molecules, not rely on PKMzeta > ZIP induced loss of spatial avoidance memory - animals injected with ZIP -> no memory - animal is caught almost-immediately back in the danger zone => Blocking LTP maintenance seems to erase spatial memory