IUBio Biosequences .. Software .. Molbio soft .. Network News .. FTP

long term potentiation

Hemidactylus at my-dejanews.com Hemidactylus at my-dejanews.com
Wed Oct 21 18:45:29 EST 1998

In article <362D2136.DD2A4A84 at pop3.concentric.net>,
  kkollins at concentric.net wrote:
> Sturla Molden wrote:
> > There is no evidence that LTP is a naturally occuring
> > phenomenon.
> Would you care to square this with what I posted in respons
to Walter, above.
> The research report I read did clearly state that Ca(2+)
dynamics above a
> threshold have "staying power" (my words)... that is, their
effects continue
> after the sub-threshold ionic flow has ceased. What, if
anything but an
> LTP-like effect, is this?

There should be a distinction made between facilitation (due possibly to
residual CA++ (or inositol mediated release from ER stores?)) and varying
degrees of potentiation, based on the time interval involved. "staying power"
is a relative term. Tetany might bring us into the interval known as
post-tetanic potentiation (PTP). I have a curiosity about whether LTP is
nothing more than an artificially induced phenomenon with no correlate in
natural systems. I think critique of LTP is good.

> > It araises from repeated tetanisation of
> > specific neural pathways, eg. in the hippocampus. It is
> > also not a homogenous phenomenon, there are several
> > sub-types of LTP depending on different receptors
> > (eg the NMDA receptor, opioid receptors, mGluRs)
> > and with different durations.
> >
> > LTP depend on the same mechanisms that seem to be
> > involved in memory formation, but there is no evidence
> > that LTP is the substrate for memory.
> Yeah, but show me "memory" without the involvement of LTP...
only way one can
> is to show me a "corpse" (brain dead).

I am presently in search of references that critique the use of LTP as a
model for vertebrate memory processing. Anybody know where I can find some
good ones? Perhaps LTP is a good model for memory processes, but I would like
for someone here to give a serious critique.

> > Theoretical models of associative memory are very
> > robust with respect to the choise of plasticity
> > mechanism, and a number of different mechanisms
> > will do the job equally well. Neurons do also
> > express different types of plasticities, not just
> > linear scaling of synaptic weights.
> Of course, it's kind of hard to "draw a picture" using only
"straight lines".

I'm not sure what is meant here. There is a great deal of complexity
associated with the LTP phenomenon. I've read discussions of everything from
NMDA receptors, calcium/calmodulin dependent protein kinases (which might
impact synapsin presynaptically and have other effects postsynaptically), NO
synthase (which interestingly is related to an epithelial enzyme and also to
an enzyme that mediates neutrophil/macrophage activity), and metabotropic
glutamate receptors that could act via an inositol (or diacylglycerol?)
pathway. I've posted about a study that looks at cell adhesion molecules.
With all these various components implicated, it is hard (for me) to arrive
at a good signal/noise ratio wrt LTP. Perhaps this will subside as I delve
deeper into all central and ancillary issues. With  an integrated approach
that includes all the putative components in LTP (a phenomenon marginally
related perhaps to memory processes in the hippocampus) it is quite hard to
draw straight lines. It is easier to pick out specific components (e.g.-NMDA
receptors and protein kinases) and ignore the other stuff. I am interested in
the cell adhesion molecule aspects though.

> > There is no reason to believe that Altzheimer patients
> > have impaired memory because they lack LTP. If they
> > do lack LTP, one should rather say that they are
> > impaired on synaptic plasticity.
> This can't be said... all that can be said is the hypothesis
must be tested
> if anything's to be said.

The transgenic study I've looked at ties an amyloid protein expression to
deficits in LTP. What implications this has are sketchy at best. It is an
interesting possibility though, that memory related dysfunction in AD
patients MIGHT be related to LTP deficits. But I admit this assumes both that
LTP=memory and that AD has an effect on LTP in human patients.

> > The hypothesis LTP = memory is far from proven.
> Has anyone in this thread said such?
I'm looking for references (hint,hint:-)). It would be a good
side issue to discuss, the critique of the notion that LTP and
memory have a significant overlap.
> > It is supported by virtually no experimental
> > evidence. I do think it is more likely that LTP
> > is an emergent phenomenon araising from massive
> > recruitment of neural plasticity apparatuses
> > due to the teanising stimuli; the real mechanisms
> > of memory - which is the natural output from
> > the cellular pasticity apparatuses - are small
> > and inconspicous.

Here is where I would ask whether convergence of presynaptic input onto a
postsynaptic neuron is analogous to the tetanization or theta bursts used in
experimental LTP induction. If this putative convergence can bring about
similar results (e.g.- depolarization to a potential that alleviates the
magnesium block on the NMDA receptor) then we have a good point for further
discussion. In this case an LTP or LTP-like phenomenon might be involved in
natural synaptic activity of hippocampal areas implicated in memory
processing. Of course this assumes LTP = memory and that memory and a certain
region of hippocampus are related.

> But they're all that's necessary... and how could they
possibly be isolated
> from LTP, therefore "making" LTP to be as you say?

Can said synaptic plasticity be broken into relatively discrete components
(e.g. facilitation versus potentiation). Remember the temporaldistinctions
also. Plus would these "discrete components" be relatively independent of
eachother? Or would one set the stage for the next?

> > And as long as single-unit studies show several
> > mechanisms of plsticity in single cortical neurons
> > and the theoreticl models work equally well with
> > a number o diffferent forms of plsticity, there
> > is no reason to suspect that Altzheimer's
> > patients are impaired on memory because they are
> > impaired on LTP.

I still would like some good references that critique the LTP = memory
notion. I've been too busy over this last week to study LTP, but this weekend
I'll dive deeper into the literature and complex issues.

> It must be tested before such can be said.
Agreed. I've had trouble finding anything that discusses LTP
and AD in the same breath, besides a couple transgenic model
> > It is just as possible that
> > they are impaired on LTP because they are
> > impaired on memory (neuronal plsticity).
> I don't disagree with you on this last point, but it, too,
must be tested.
I'll get back into this thread over the weekend. Everybody's
input has been very helpful.

Scott Chase (note followups at anthym at webtv.net)

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