Conditioning?

Lewis J Herberg skgtljh at ucl.ac.uk
Wed Nov 3 14:13:27 EST 1993


Bill Calvin writes that for LTP, NMDA and all that "life is complicated". 
This is perhaps an oversimplification.

He and Bill Skaggs play down the role of glycine at the NMDA receptor site,
apparently on the strength of (in vitro) evidence that ambient levels of
glycine exceed the level needed for full occupancy of the recognition 
site. Nevertheless there are several remarkable reports claiming positive
nootropic effects after in vivo administration of glycine agonists. One
explanation could be that glycine concentrations may be lower at the
synapse than elsewhere (because of local uptake).

And the horde of co-factors regulating the NMDA complex grows continuously.
Putrescine and spermidine are mysterious polyamines with facilitatory
and inhibitory influences. A phencyclidine-semsitive site responds to
various toxic and/or recreational compounds including ketamine, a
well-known cough mixture, and to a (proposed) endogenous ligand. The
associated Cl channel is independently modulated by Mg ions. There is
a newly-described redox dependent site. The receptor may be subject to
negative feedback by niitric oxide. The receptor probably
exists in at least two broad classes or states...

It wd nice to link kindling to LTP or to memory but (IMHO) the
weight of evidence so far is for non-specific, pathological changes.
The effects of kindling on polyamine synthesis, catecholamines,
amino acid transmitters and brain microstructure have been and
are being intensively studied but as far as I know without
robust suggestive results.

Jack Herberg (L.Herberg at ucl.ac.uk). Institute of Neurology London 



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