X-Message-Number: 8412
Date: Mon, 21 Jul 1997 09:53:16 -0800
From: "Joseph J. Strout" <>
Subject: Re: synapses and LTP

In Message #8405, Brian Rowley <> wrote:

>As far as electrophysiologists know, LTP (long-term potentiation) is
>permanent (i.e., "indefinite").

...where "indefinate" is defined as "an hour or more".  It's a big leap
from this to lifetime memories.  LTP is poorly understood still; there are
apparently effects both pre- and post-synaptically, and teasing apart the
roles of the various components has been tricky.  But none of the
components I've read about are appropriate for very long-term memory
storage.  A recent review (Science 276:2001-2002) tried to show that the
primary effect is mediated by postsynaptic  calmodulin-dependent protein
kinase II (CaM-KII).  CaM-KII is initially activated by calcium, and may
maintain its activity by an autophosphorylation feedback loop.  Activated
CaM-KII, in turn, increases the sensitivy of neurotransmitter receptors at
the synapse.

While this seems like a reasonable way to adjust the efficacy of a synapse
for a few minutes to hours, it's unlikely to underlie memories that last
years.  First, LTP is only induced by highly artificial stimuli; it may be
more of a homeostatic mechanism than a day-to-day learning mechanism.
Moreover, it is lost as quickly as it is gained; it lasts hours only when
normal stimulation is minimal.  Finally, other research has shown that
long-term memory is associated with the formation of new synapses, and the
retraction of old ones; and that this is necessary for learning (if you
block protein synthesis, you can still get LTP, but you can't form new
long-term memories).  I think the growth and retraction of synapses is a
much more likely substrate for long-term memory.  LTP most likely serves as
either a homeostatic mechanism, or a temporary memory mechanism used as the
first stage of a more dramatic physical reorganization.

,------------------------------------------------------------------.
|    Joseph J. Strout           Department of Neuroscience, UCSD   |
|               http://www-acs.ucsd.edu/~jstrout/  |
`------------------------------------------------------------------'

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