LTP and Spatial Learning Flashcards
Potentiation definition
the increase in strength of nerve impulses along pathways that have been used previously, either short-term or long-term. In the brain this is relatively long-term
Collingridge, Kehl & McLennan (1983)
blocking NMDA receptors before induction impairs LTP, but not after induction
Hippocampus use in LTP studies
Given that many of the demonstrations of LTP have been in hippocampal cells and the hippocampus is known to be important for spatial learning then a good place to start would be to see if hippocampal LTP is necessary for spatial learning
AP5
The drug AP5 is an NMDA antagonist that impairs LTP
Morris et al 1982
rats with hippocampus lesion show no spatial learning. LTP in hippocampus necessary for learning
Morris 1989
AP5 impaired rats show no preference for old quadrant whereas control rats do. Also show a slower latency. However they are also clumsier. drug treated rats can learn a visual discrimination normally in the water maze showing that AP5 doesn’t impair all behavior in the water maze. This may suggest that the deficit on the spatial task is selective. However, what if the visual discrimination is just easier than the spatial task? Would this mean that it is not a fair comparison?
Morris et al. (1990)
if rats learnt a spatial task and were then given AP5 they were not impaired. Therefore, AP5 does not impair performance or expression of previously acquired learning. However, if the drug treated rats were required to learn a new spatial location in the pool then they were then impaired. This suggests that AP5 only impairs initial learning. This is consistent with our hypothesized role of the NMDA receptor; it is necessary for LTP to take place. Importantly, once again, AP5 spares performance of some spatial tasks but impairs new learning, suggesting that any impairment caused by AP5 is not simply due to some global sensorimotor disturbance.
Bannerman et al. (1995)
If rats have had experience of learning a spatial task, subsequently learning a new spatial task doesn’t require NMDA receptors. showed that if rats had learnt the water maze task in one room and then were drugged and required to learn the task in a new room (with distinct spatial cues) then they were not impaired.
Steel and Morris 1999
trained rats to swim to a submerged platform, however, the platform location would change session-to-session, but not within a session. Rats managed to learn the new location of the platform within one trial. This can be seen by the difference in latency between trial 1 and trial 2. AP5 impaired performance when the interval between trial 1 and 2 was 20 minutes or more, but not when it was 15 s. This suggests that AP5 impairs long-term retention of new learning, but spares short-term retention. The fact that drug treated rats were normal when the interval was short makes it hard to explain the impairment at longer intervals in terms of a sensorimotor deficit.
Is LTP not the basis of learning?
it may simply mean that NMDA receptors in the hippocampus have a more selective role in spatial learning than maybe we first imagined
Problems with using AP5
effect NMDAR outside the hippocampus
cause ataxia
change in motivation state less anxious)
cause weight loss
NMDA receptors
four subunits, all contain NR1 (which is obligatory)
Tsein et al 1996
tested KO NR1 in CA1 region of hppc. mice. Performed poorly on water maze but also on visual discrimination. How can we be sure their impairment isn’t due to some global sensorimotor problem?
Tang et al 1999
Doogie mice that overexpress the NR2B subunit of the NMDA receptor. More NR2B means more LTP. These mice showed enhanced learning in the Morris water maze and showed enhanced object recognition. It is hard to imagine that a non-specific, sensorimotor deficit would result in this pattern of performance? This means that LTP may be important for learning
von Engelhardt et al. (2008)
NR2B KO mice. mice were not impaired on acquisition of the water maze and when the performance of the probe task was worse when it was broken down into time bins. Showed impaired spontaneous alternation in t maze.
