Biological 3: Spatial learning and LTP 2 Flashcards
(15 cards)
At what mv of depolarisation is the magnesium ion in NMDA receptors ion channels released?
Around -20 to -40mv
This is near the action potential threshold (around 55mv)
What is memory the result of at a cellular level
Some growth process or metabolic change at the cellular level
What is useful about hippocampal circuitry?
The circuit structure of neurons means we can look at distinct neurons
What happens to the EPSP after LTP has occurred?
It increases
Does LTP happen in single synapses?
No - happens in populations of cells - many synapses
What is the induction mechanism in LTP?
The NMDA receptor
What are the side effects of AP5? (NMDA receptor antagonist drug)
- effect on NMDAR outside the hippocampus
- cause ataxia (motor impairments)
- change in motivation state (less anxious)
- cause weight loss
What alternative technique can be used to avoid issues with pharmacological manipulation of LTP? (AP5)
Genetic manipulations
- The function of the NMDA receptor can be directly manipulated: deleting the gene responsible for receptor subunits.
- Genetic manipulations can be targeted to particular brain areas with greater accuracy than drug manipulations.
What was the genetic manipulation in Doogie mice?
A subunit of NMDA receptor (NR2B) was over-expressed
This meant that more calcium could enter the cell, so LTP was enhanced
How were abilities different in the transgenic NR2B Doogie mice compared to control mice?
Enhanced learning in the water maze - typical mice gets good after 6 sessions, doogie mice get good after 3
Enhanced memory of the platform location
Enhanced object recognition memory (preference for novel object - shows memory of previously shown object)
Enhanced fear memory - longer duration than controls (contextual and cued)
Enhanced extinguishing speed of associations that no longer exist
What was a possible side effect of NR2B over-expression in mice?
Chronic pain (some reports)
How is LTP genetically knocked out?
The NR1 subunit is obligatory for NMDA receptors - if this is knocked out then NMDA receptors do not function and LTP is impaired.
Mice with this genetic knockout are called Grin1ΔDGCA1 mice. They have knocked out NR1 subunits in the dentate gyrus & CA1 (hippocampus).
Bannerman et al. (2012) trained control and Grin1 mice on a variant of the water maze task.
Two identical beacons were in a pool - one signalled location of the platform, the other did not.
Beacons could only be distinguished by extra-maze cues.
Over trials of training mice were placed into the pool at locations that were nearer to the incorrect beacon or nearer to the correct beacon, or equidistant between the two beacons.
What were the results?
When released from a starting point that was equidistant between the two beacons (or a point near the correct beacon) the knockout mice were not impaired, demonstrating normal spatial learning.
When release from a starting point near the incorrect beacon (S-) the knockout mice made more errors than the control mice.
The knockout mice could not inhibit the response to approach the incorrect beacon.
At the end of training the beacons and platform were removed a probe test was performed.
The control and knockout mice showed a strong preference for the quadrant of the maze in which the platform was previously located.
Shows that they have learnt location of platform, know which beacon signals it, but they cannot inhibit response
What did Bannerman’s 2012 study with the two beacons indicate about the role of NMDA receptors/LTP?
NMDA receptors in the hippocampus are important for inhibiting responses to ambiguous cues (approaching a beacon is correct only 50% of the time).
NMDA receptors do not appear to be essential for spatial learning.
However, they do appear to be important in some way for spatial behaviour
What is Gallistel and Matzel’s position on LTP and learning?
LTP and learning are not similar.
Timing of events: LTP – milliseconds; Associative learning – seconds, minutes, hours
Persistence: LTP is long lasting, but not long-term; Associative learning is long-term (lasts indefinitely)
Reacquisition: associative learning is reacquired more rapidly than initial acquisition, and neural mechanisms do not match this
