Received: by alpheratz.cpm.aca.mmu.ac.uk id UAA09459 (8.6.9/5.3[ref pg@gmsl.co.uk] for cpm.aca.mmu.ac.uk from fmb-majordomo@mmu.ac.uk); Sun, 6 Aug 2000 20:56:53 +0100 To: memetics@mmu.ac.uk Date: Sun, 06 Aug 2000 12:45:51 -0700 From: "Scott Chase" <hemidactylus@my-Deja.com> Message-ID: <PGFIMNPBIFENGCAA@my-deja.com> X-Sent-Mail: off X-Mailer: MailCity Service Subject: RE: Simple neural models X-Sender-Ip: 209.240.220.193 Organization: My Deja Email (http://www.my-deja.com:80) Content-Type: text/plain; charset=us-ascii Content-Language: en Content-Length: 7403 Content-Transfer-Encoding: 7bit Sender: fmb-majordomo@mmu.ac.uk Precedence: bulk Reply-To: memetics@mmu.ac.uk
--On Sat, 05 Aug 2000 18:43:57 Mark M. Mills wrote: >At 06:38 PM 7/25/00 -0400, I wrote: > >I'm not suggesting an entire nerve cell takes on a single binary state, > >only that binary elements at the synapse level play key roles in > >electro-chemical signal processing. Specifically, I'm alluding to > >Kock's description of autophosphorylating kinases (Biophysics of >Computation). > >He suggested they are analogous to transistors. With a certain amount of > >voltage applied to them, they conduct. Without the voltage, they resist. > >Derek disputed my interpretation of autophosphorylating kinases, so I wrote >Koch for clarification and received the following reply: > >"yeah, a kinease is just a specific type of enzyme, so they don't conduct >electricity. So in that >sense your neurology pal is correct. Think of the autophosphorylation like >a button. You can press >it in with your finger and it remains in its depressed position until you >press it again and it >pops back to its original state. A neat molecule." > >In reply, I asked for his opinion on the role autophosphorylating kinases >play in signal processing, but haven't received any answer. > >After reading the Koch Lab's website (http://www.klab.caltech.edu/), I >contacted Gabriel Kreiman. According to his website, he had done some work >with kinases. I asked him if he could relate kinases to signal >processing. He replied: > >"The role of kinases in signal processing is still unclear. >They are known to be involved in memory potentitation processes." > >He pointed me to the paper: 'Tetanic Stimulation Leads to Increased >Accumulation of Ca++/Calmodulin-Dependent Protein Kinase II via Dendritic >Protein Synthesis in Hippocampal Neurons (1999) >(http://goethe.klab.caltech.edu/~gabriel/publications/camkii1.html)' >Kreiman coauthors. > >Additionally, 'Long-Term Potentiation: What's Learning Got To Do With It?' >by Tracey J. Shors & Louis D. Matzel (1997) >http://www.cogsci.soton.ac.uk/bbs/Archive/bbs.shors.html >has an interesting survey of work on memory models, including suggestions >that kinases are involved. > If I'm not mistaken, the main jist of this article was a critical review of notions about long term potentiation being *the* underlying mechanism of learning and memory. There seems to be a strong conceptual connexion between LTP and learning/memory in the vast LTP literature and Shors and Matzel took inventory of this and suggested alternative notions of their own (IIRC LTP related to attention or arousal). For some reason, I want to invoke the old correlation versus causation problems here.
They also looked at the problems with establishing what LTP precisely encompasses and falsification problems which arise from LTP's status as an explain all phenomenon. I'm not familiar with a majority of the LTP literature, but I recall some key articles which may be of interest. I need to rephotocopy many of the articles I used for a presentation a couple years ago in a neuro class and gave to my professor for her future use. The Bliss and Lomo (1973) article which I think is referenced in Shors ans Matzel is probably what can be thought of as the fountainhead. Later workers harkened back to Hebb's monograph (also cited by Shors and Matzel IIRC) where his synaptic efficacy postulate stems from. For a review which is complementary to Shors and Matzel (ie- I think it was less critical of LTP as a putative memory model) try:
Bliss TVP and Collingridge GL. 1993. A synaptic model of memory: long term potentiation in the hippocampus. Nature (361): 31-9
Again, the literature on LTP is vast and extends over several decades. More recent work has utilized genetic knockouts. There may still be some problems in what can be assumed based on these sophisticated studies.
The Shors and Matzel article above can be found in a journal:
Shors TJ and Matel LD. 1997. Long-term potentiation: what's learning got to do with it? Behavioral and Brain Sciences (20): 597-655
The reason I say this is because there are several commentaries in response to this article that follow in this journal including:
Gerlai R. 1997. A causal relationship between LTP and learning? Has the question been answered by genetic approaches? Behavioral and Brain Sciences (20): 617-8
Gerlai's abstract:
(bq) "Gene targeting has generated a great deal of data on the molecular mechanisms of long-term potentiation and its potential role in learning and memory. However, the interpretation of some results has been questioned. Compensatory mechanisms and the contribution of genetic background may make it difficult to unequivocally prove the existence of a causal (genetic) link between LTP and learning." (eq)
There are other commentaries following Shors and Matzel's article which may be of interest. The one point that I remember from Shors and Matzel's article was the invoking of the "search for the engram" phrase, which brings me back to earlier posts of mine about terminological clashes. If the engram is a term of choice amongst some memory researchers, then why butt the meme up against it as a replacement term? I notice that Aaron Lynch uses the term mnemon which is similar to engram in being a unit of memory or akin to a memory trace and with a history of its own though probably not as popular as the engram.
Nonetheless, anyone interesed in internalizing memetics by bringing the field in line with memory research will inherit many of the same problems, I guess, as memory researchers, plus adding the specifics which are peculiar to memetics itself. Here we also look at the other "way of seeing" or externalist perpective (ie- Gatherer if I'm not mistaken) which would focus on cultural aspects more than neural aspects*. Somewhere a bridge exists... > >Based on all this additional input, I want to thank Derek for pointing out >the errors in my characterization of autophosphorylating kinases. We don't >know what they do. We only know they are involved in neural processes and >flip/flop between two stable states at a speed about as fast as the >quickest reflexes. > > My main qualm would be why the focus on the kinases alone? If you read the critical Shors and Matzel article, you will notice the other putative components involved, including the NMDA receptor and also the retrograde transmitter such as nitric oxide (NO). When I was more in tune with this LTP stuff for my presentation, I focused on some recent articles on the NMDA-R and the calcium calmodulin kinase. I only read about NO here and there, but I recall some workers have focused on it.
There are other putative molecular components to memory and to reduce everything to the "one true molecule" *may* present problems, though I can see that simplification is also important for modelling sake. I'm not familiar with the specialized biophysical and electrochemical details of the kinases, so I'm of no use here. I wouldn't mind learning though, but one must exercise extreme caution when treading on specialzed fields of research and trying to bring key points back into a multidisciplinary field such as memetics. That's why I assume my above reply to be nothing more than sheer jibberish :-)
*-not to mention the culturgens
Scott
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