Synaptic modification rules ?
nettron2000 at aol.com
nettron2000 at aol.com
Wed May 19 23:12:45 EST 2004
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
> 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.
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.
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