Synaptic modification rules ?

[nettron2000 at aol.com]

Matthew Kirkcaldie <m.kirkcaldie at removethis.unsw.edu.au> wrote in message news:<m.kirkcaldie-336F6F.10474119052004 at tomahawk.comms.unsw.edu.au>...
> In article <ec29a509.0405181329.2a3c48a7 at posting.google.com>,
>  nettron2000 at aol.com wrote:
> 
> >  Matthew,could you please explain further what you meant by "As far as
> > "rules" go, there are no rules, just consequences of particular firing
> > patterns for cells which have particular membrane properties and
> > biochemistry."
> >  Are you saying that the spike firing pattern determines the mechanism
> > ( or means) used for modification ? In otherwords, if a particular
> > firing pattern is present in a cell assembly then some , as yet,
> > imagined molecular mechanism "kicks-in" and modification takes place ?
> > If not ,well, sounds interesting. :)
> 
> It's not imagined - many of the molecular details are actually quite 
> well known and have been experimented on.  In general, the main process 
> is that patterns of firing in pre- and post-synaptic (receiving) cells 
> combine to allow calcium entry to the post-synaptic cell via the NMDA 
> receptor.
> 
> Excitatory synapses in the central nervous system usually use glutamate 
> as a neurotransmitter.  Release of glutamate causes sodium ions to enter 
> the post-synaptic cell via glutamate receptors, which are ion channels 
> that open when they bind to a glutamate molecule. The two main glutamate 
> receptors are AMPA and NMDA (named for chemicals which were found to 
> activate them in pharmacological studies). The entry of sodium ions 
> depolarises the membrane, which makes the post-synaptic cell more likely 
> to fire, depending on the amount of sodium which enters and hence the 
> size of the depolarisation.  If you want to change the strength of a 
> synapse, you have to change the amount of depolarisation it produces.
> 
> The NMDA receptor is a glutamate-activated channel which allows sodium 
> *and* *calcium* into the postsynaptic cell when it binds to glutamate; 
> however, it is normally blocked by being bound to a magnesium ion. If 
> the post-synaptic cell fires, however, the magnesium is displaced, and a 
> subsequent release of glutamate at the synapse, within a defined time, 
> will allow calcium to enter the postsynaptic cell. Calcium is a very 
> potent activator of kinases and phosphatases, enzymes which act to 
> chemically activate/deactivate other proteins in the near vicinity. 
> Depending on the timing relationship between successive firings, 
> calcium-dependent kinases and phosphatases are activated and in turn 
> activate or deactivate mechanisms which cause endocytosis (removal of 
> membrane from the surface) or exocytosis (fusion of internal membrane 
> packages with the surface membrane). The membrane which is removed or 
> added is packed with AMPA receptors, which are sodium channels activated 
> by glutamate in the synapse.
> 
> The more AMPA receptors, the more channels to permit sodium entry when 
> the synapse fills with released glutamate.  That means a given release 
> of glutamate will have a greater or lesser effect on the postsynaptic 
> cell depending on whether AMPA receptors have been added to, or removed 
> from, the post-synaptic membrane.
> 
> Thus glutamate at the NMDA receptor will, according to the recent 
> activity of the postsynaptic cell, allow a little burst of calcium to 
> enter the post-synaptic cell at a certain time after its activity.  
> Depending on the timing this will activate biochemical pathways which 
> cause AMPA receptors to be added to or removed from the membrane, which 
> alters the strength of the synapse.
> 
> Of course this is a simplified picture.  Most of the enzymes involved in 
> moving the receptors are known or strongly hinted at, but any other 
> biochemical interaction with these processes will also alter the 
> receptor trafficking (as it is called) and hence synaptic modification 
> processes.  Have a look at a 2002 review by Malinow and Malenka in Ann 
> Rev Neurosci 2002;25:103-26 if you would like (A LOT) more detail!
> 
> > BTW, thanks, eagerly await your reply.
> 
> My pleasure, I tend to run on a bit though I'm sorry.
> 
>       Cheers,
> 
>          Matthew.



 No need. Not run on at all, quite informative and interesting, some
of your text leapt out especially when you mentioned AMPA and NMDA
receptors, had jotted that down a few nights earlier. But first ive
heard how they (AMPA, NMDA)were removed from or added to the membrane
as a function of timing, interesting indeed.
I can see how this would modify the integrate and fire properties, as
well as the time constant of the neurons but i guess what im getting
at is more of the WHY of it. To use the cerebellum as an example: some
experimental evidence ive rea about suggests that climbing fibers from
the inferior olive "allow" modification to occur on the parallel
fiber-purkinje cell synapses when certain conditions exists,
signifying that either an error as occured and the neuron needs
updating or the end of a movement/motor program is eminant.I guess
this is more in-line to what i mean by "rules".

 Neuron function alone has proven to be rather difficult to pindown (
atleast for me) and neuron learning concepts nearly in-excessable due
mainly to the lingo used, lack of good lay-person reading material or
buried in advanced mathematics.

 Thanks Matthew, i'll look into the reviews you suggested as well as
those suggested by others.