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/ | `------------------------------------------------------------------' Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=4994