Synaptic modification rules ?
m.kirkcaldie at removethis.unsw.edu.au
Tue May 18 19:47:41 EST 2004
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
> 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.
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