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LTP in hippocampus

Bill Skaggs bill at nsma.arizona.edu
Wed Nov 1 17:25:44 EST 1995

kevin at gaba (Kevin Hellman) writes:
   > I have attached some citations... Although, I am not an
   > experienced physiologist, I am skeptical about the role ltp in
   > the hippocampus.  The paradigms used require an unusual amount of
   > stimulation.  LTP might be a form of learning, but is it really
   > the form of learning we use in our hippocampus?

There is an explanation for the high level of stimulation required
using the standard paradigm.  The pathways that are commonly
stimulated in LTP experiments evoke direct excitation, but they also
excite interneurons and thereby evoke feedforward inhibition.  The
driving of interneurons is very fast, and much stronger than the
driving of principal cells.  Consequently, at low levels of
stimulation, the feedforward inhibition of principal cells outweighs
the direct excitation, and no LTP occurs.  In many parts of the
neocortex and hippocampus this occurs at ALL levels of stimulation,
and no LTP occurs regardless of how large the stimulus is; but LTP can
be obtained by pharmacologically blocking inhibition.  In the pathways
where LTP can be obtained without such measures, the level of
feedforward inhibition saturates at a certain stimulus intensity,
while the direct excitation keeps increasing.  Eventually the
excitation outweighs the inhibition, and enough postsynaptic
depolarization occurs to permit LTP.

This typically requires extremely strong stimulation, but only because
the pattern of stimulation (many fibers activated all at once) is not
the sort that the system is built to work with.  It has now become
clear that all that is really required for LTP to occur at a synapse
is a burst of presynaptic activity in conjunction with strong
postsynaptic depolarization.  This occurs quite often in the naturally
functioning hippocampus, but because of the feedforward inhibition it
is difficult to bring about by artificial stimulation.

In any case, there are now known to be ways of getting LTP that don't
require such massive stimulation.  One of them is the so-called "theta
burst" paradigm, in which a single moderate stimulus is applied,
then, after a 200 millisecond pause, a brief train of moderate
stimuli.  This works because the first pulse puts the inhibitory
interneurons into a refractory state that persists for a few hundred

	-- Bill

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