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Bill Skaggs bill at nsma.arizona.edu
Tue Nov 2 23:33:40 EST 1993

wcalvin at stein2.u.washington.edu (William Calvin) writes:

   bwhite at oucsace.cs.ohiou.edu (William E. White ) writes:
   >I was under the impression that glycine was required for the NMDA channel
   >to operate.  Is this in fact true?

   Glutamate is the transmitter at NMDA synapses. N-methyl-D-aspartate is 
   merely the most efficient molecule to open those channels, but isn't the 

Quite right, but there's a little more to the story.  The NMDA
receptor *does* have a glycine binding site, and glycine *is*
necessary for the channel to open.  But my understanding is that
glycine is usually present in the extracellular medium in high enough
concentration for the glycine binding site to be almost always
occupied.  So it is required, but may not be functionally relevant.
(But then why is the binding site there in the first place?  Hmmm . . .)

   >Is there any mechanism yet for memory lasting beyond several days, and
   >more importantly for converting LTP into this type of memory?

   Changes in the size of individual synaptic endings, and in the number of 
   them per pre-post cell pair, are possibilities with evidence elsewhere.  
   For LTP, life is complicated.

Another interesting possibility is a mechanism called "kindling",
usually studied in connection with epilepsy.  The synaptic events
involved aren't clear, but there is some evidence that they include an
increase in the strength of excitatory synapses.  Anyway, kindling is
induced by repeatedly stimulating certain brain pathways at moderate
intensity, with long delays between stimuli.  Once a day for several
days is a common schedule.  The stimuli have have to be strong enough
to cause "afterdischarges", which means cell firing that outlasts the
stimulus itself.  What happens is that the responses to the stimuli
gradually increase in size, eventually developing into full-blown
seizures.  The crucial point is that the increased responses caused by
kindling last for a very long time, years in some cases.

	-- Bill

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