genetic control of inter-neuron signals

NMF nm_fournier at
Thu Apr 1 22:23:43 EST 2004

R Norman and Sandy Hodges:

I found your post to be quite interesting.  After reading Sandy Hodges
original comment and your response, this whole discussion made me think of
George Ungar's work on "scotophobin" from the 60's and 70's.

Briefly in these experiments, donor rodents were trained in a task, such as
avoiding a dark region associated with an aversive stimulus.  Following this
conditioning paradigm, the brains were removed, homogenized, and processed
in order to remove the small protein fraction.  This "sample" from the
donors was then injected into the brains (and/or bodies through systemic
routes, as was done in later studies) of recipient rodents.  When these
recipient rodents were placed into the training situation, they avoided the
dark area even though, for them, the aversive stimuus was never paired
previously.  These findings led to the concept of "transfer of learning".

(The actual protein sequence was later isolated and was found to be 15 amino
acids in length, i.e. a pentadecapeptide, that was later called
"scotophobin.  Moreover, when made synthetically and injected into rodents,
the same behavior was also elicited.)

Although these findings were quite controversal and well debated, in any
case, many researchers did find similar findings. It seems to me at least,
that these original studies lost a lot of magnitude after Bliss and Lomo
work in the 70's showing that the Hebbian concept of long term potentiation
was operating within the hippocampus and could be a correlate of learning
(after the influence of Lynch and Baudry).

The only reason for why I bring this rather old controversal study up is
that Ungar and other researchers speculated that this actual protein
sequence might get incorporated into the cell and directly influence the
genetic machinery of the nucleus, ultimately leading to changes in the
extent of protein synthesis.  In any case, these original concepts were
quite revolutionary (even though the actual basis behind the effects might
of have been wrong) in that they highlighted the importance of the
postsynaptic interactions at the level of the nucleus.  Moreover, Ungar did
suggest that these subsequent nuclear-mediated influences might direct
subsequent protein synthesis leading to synaptic modifications in a manner
that might correlate with the 'transfer of learning'.

Although these findings were heavily debated they were never really followed
up after the 1970's.   In any case, I thought it might be an interesting
point to bring up, especially since it is quite possible that this compound
might have a directed influence and impact upon the nuclear domain.
(Perhaps the effect is similiar to the indirect action that hormones have on
nuclear-mediated signalling cascades?)

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