X-Message-Number: 4994
Date: Sun, 15 Oct 1995 19:35:54 -0700 (PDT)
From: Joseph Strout <>
Subject: Re: Request for help (#4987)

Yesterday, Mike Darwin requested input on a difficult case.  The 
patient's brain has been undergone fixation and prolonged storage at 
4'C.  Her treatment (as I understand it) can be summarized as follows:

	24H in air at 4 C
	30H in formalin at 4 C
	4 weeks in saline at 4 C
	1 day in formalin at 2-4 C
		(tissue found to be very firm at this point)
	to present in SHP-1 + 2% glute

He then writes: 

> My professional opinion is that the *best* that can be said about this 
> patient's prospects for recovery with declarative memory/former identity 
> intact are that they are vanishingly small.
>	...
> Input from Joe Strout and others involved in investigating the neurobiology 
> of memory and learning as active researchers are especially welcomed.  If 
> we could better guess what we can likely SAFELY "afford to throw away" 
> (i.e., dissolve or elute) that would be useful information.

My ignorance has never weighed so heavily on me as today.  But, I suppose 
we must all do the best we can, and since my input was directly 
solicited, I will offer what insight I have.  Please understand that my 
education is only beginning, and most of my knowledge is second-hand.

First, I think the most troublesome period is the first: a day in air at 
4 C.  The temperature alone will not prevent massive degeneration, and 
after 24 hours I would expect most of the fine structure to be gone.  
The subsequent fixing would of course progress from the outside in, and 
here we can at least find some hope.  Though the hippocampal/temporal 
lobe system is needed to create new long term memories (as demonstrated 
by the famous patient H.M.), the eventual site of long-term explicit  
memory storage appears to be the cerebral cortex.  We obtain best 
structural preservation by fixing with 4% paraformaldehyde plus 2% glute, 
and such tissue will last quite a long time at 4 C.  So perhaps the 
patient's long-term memory will be recoverable after all.

As for the actual substrate of those memories, the theories are various 
and I'm sure Mike knows them as well as I.  Personally, I think it likely 
that long-term memory is finally set by the creation and destruction of 
synapses (rather than, say, subtle changes in synaptic efficacy); your 
primary focus of preservation, then, should be the cell membrane.

Mike, I wish you and your patient the best of luck, and deeply regret 
that I cannot be of more help.

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