LTP and spatial learning: drug and genetic manipulations Flashcards
Who provided an example of the general idea of LTP?
Bliss & Lomo (1973) - WS=WR, SS=SR, WS=SR. Presynapstic neuron = post synaptic neuron
Where have many demonstrationso f LTP been found and what is this area said to be important for?
Hippocampus - spatial learning
What drug blocks NMDA receptors?
AP5
Who did a series of experiments involving AP5 and what did they show?
Morris (1989) - - AP5 drug treated rats = impaired performance on Morris water maze
What happened if rats were given AP5 after learning spatial task?
Morris (1990) - if given drug after learning spatial task = peformance was not impaired. However, if they had to learn new locations in pool after taking drug = impaired
What conclusion can be drawn from Morris (1990) study?
AP5 impairs initial learning – NMDA receptor = necessary for LTP to take place
Who did a contradicotry study to Morris (1990)
Bannerman et al (1995) - if rates learned water maze in one room, were then drugged, and learnt in new room - not impaired
What conclusion can be drawn from Bannerman et al’s study?
NMDAreceptors are not necessary for learning new spatial tasks
What can explain the difference in results of Morris and BAnnerman’s studies?
New location - same pool = learning to unlearn previous rule
New location - new room - learning new information, nothing blocking this learning
what conclusions can be drawn from BAnnerman and Morris studies together?
NMDA receptors are necessary for learning new locatrion in a familiar environment when the new information contradicts previously learnt spatial information
what role does NMDA recptor and therefore NMDA receptor realted LTP have on spatial learning
Might not be important/its role may be limited to particular conditions
Who came up with another condition under which AP5 effects vary?
Steel & Morris (1999) - rats - submerged platform. Location changed from session to sesion but not within. AP5 impaired performance when gap betwee ntrial 1 and 2 = >20 mins
What conclusions can be drawn form STeel & Morris experiment?
AP5 impairs retention of new learning, but spares ST retention
Why might drug manipulation not be a good test of LTP? examples…?
MAy have side effects e.g. effect NMDAR outside hipipocampus, motivational changes (less anxious) etc
How do you make a KO mouse?
Embroynic stem cells from mouse - introduce DNA contianing mutant gene. Inject altered cells into embryo - implant into surrogate mother - give birth. Mate babies - some offspring will have both copies of mutant gene = KO mouse
Experiment involving KO mice and Morris WM?
Tsein et al (1996) - mice lackiing NR1 sub-unit of NMDA receptor = impaired on MWM. Lack of NR1 = no functioning NMDA receptor
Why would you want to over express parts of MDA receptors?
To eradicate issues of non-specific effects –> to find out does enhancing LTP also enhance performance?
What are Doogie mice?
Overexpress NR2B - sub-unit of NMDA receptor.
Who did an experiment with Doogie mice?
Tang et al (1999) – Doogie mice showed enhanced learning inn Morris WM and enhance object recognition. More NR2B = more LTP
Conclusion from TAng et al experiment?
eEvidence that LTP is imporatnt for learning
Who fruthered evidence of importance of NR2B sub-unit?
von Englehardt et al (2002) – NR2B-KO mice = not impaired on acquisition of water maze. Advantage over controls on probe test too - put down to not extinguishing searching behaviour in the target quadrant. Conc - NR2B mice = impaired on everything = no normal performance on any behavioural measure
What ahppens with NR2B KO mice on T maze?
They have impaired spontaneous alternation. This involves remembering last move = memory = impaired
What are teh two errors on radial arm maze?
Spatial reference memory error and spatial working memory error
What is spatial reference meemory error?
Enter arm which is not paried with a reward
What is a spatial working memory error?
Enter arm which has been previously entered in the trial. Reflects alternation behaviour. Trial specific
What are NR1-KO mice impaired on?
Impaired on SWM. Normal SRM
What other mice have same pattern as NR1-KO. What is it?
Imparied on SWN. Normal SRM. NR2B-KO AND GLUA1-KO.
Which of SRM oR SWM is involved in associatve learning?
SRM
Who did an experiment into the differences between learninig and LTP?
Gallistel & Matzel (2012)
In what areas did Gallistel & MAtzel find differences (2012) betwen LTP and learning?
Timing
Persistnece
Reacquisition
Timing differences between LTP and learning
LTP = ms, associative earning can be secs, mins, hours
What differences did theyf ind in persistence between learning and LTP?
LTP - long lasting, not LT. Associative learning = LT (indefinately_
What differences are there in re-acquisition betwen learning and LTP
LTP - just as long/as much effort. ASsociative learning- reacuqition = more rapid than initial acquisition