LTP via NMDA in neocortex

Christian Holscher CHOLSCHR at TCD.IE
Fri Mar 22 09:31:23 EST 1996

In article <4irgg0$pn8 at>, centexchic at
(Centexchic) wrote:

> Re:  lab of Richard Morris, a paper has
> been published recently which simply states that at least spatial learning
> is most probably not dependent on LTP in the dentate gyrus and on the
> NMDA-receptor (ref. 1) [and] they show that NMDA rec. are not needed for
> learning of spatial or nonspatial tasks (ref 2)
> -First, how is a Morris water maze a test of spatial learning?  If a rat
> learns to approach a cue in the environment in order to reach a platform
> and be removed from the water, how is that a spatial memory.  It is simply
> an approach to a stimulus.     
> -Secondly, treatments which are known to affect the NMDA receptor do not
> affect all types of learning (e.g. ethanol administration during
> development).  It is by no means safe to say that the NMDA receptors are
> not needed for nonspatial tasks.  How do you explain a deficit on the
> patterned single alternation task after MK-801(NMDA noncompetetive
> antagonist) administration?  If LTP is truly Ca2+ dependent and reliant on
> the NMDA receptor, then by blocking the Ca2+ channel, you should be
> blocking LTP (didn't Morris also show this using AP5 and his Morris water
> maze too?)

To 1: Well, I do not think you can get away that easily. Even though there
has been some questions to what extend water maze tasks contain nonspatial
components that make laerning difficult for animals which are otehrwise
fine in their spatial learning abilities. The Bannerman, Morris et al.
paper you quoted suggests this. If the animals can't learn the task after
AP5 injections but can learn the task after spatial pre-training and AP5
injeciton then something is wrong here. It could be that the animals are
too scared at first and can't learn the task very well, but after the
pretraining they are familiarized enough with the task and relax more
(just a suggestion).
However, it is hard to see how the task canNOT be a spatial task. The
animals have to find the invisible platform and learn the general location
of it after some trials.  "It is simply an approach to a stimulus."  is
not good enough to explain the problem in this task!

To 2: Sure, the paper does not claim that NMDA receptors have nothing to
do with any kind of learning. There might well be learning problems that
involve NMDA rec. during memory formation. Morris et al. only showed that
you can block LTP in vivo with AP5 but spatial learning is not impaired. 


Christian Holscher, PhD
Trinity College Dublin
Dept. Pharmacol. & Therapeutics

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