Received: by alpheratz.cpm.aca.mmu.ac.uk id IAA06768 (8.6.9/5.3[ref pg@gmsl.co.uk] for cpm.aca.mmu.ac.uk from fmb-majordomo@mmu.ac.uk); Wed, 26 Jul 2000 08:30:52 +0100 Message-ID: <A4400389479FD3118C9400508B0FF230040E6A@DELTA> From: "Gatherer, D. (Derek)" <D.Gatherer@organon.nhe.akzonobel.nl> To: "'memetics@mmu.ac.uk'" <memetics@mmu.ac.uk> Subject: RE: Simple neural models Date: Wed, 26 Jul 2000 09:26:53 +0200 X-Mailer: Internet Mail Service (5.5.2650.21) Content-Type: text/plain; charset="iso-8859-1" Sender: fmb-majordomo@mmu.ac.uk Precedence: bulk Reply-To: memetics@mmu.ac.uk
Mark:
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:
I don't understand what you mean by 'With a certain amount of voltage
applied to them, they conduct'. You must mean transistors? Surely not the
kinases. Kinases add phosphate groups to proteins - if they are
autophosphorylating, they add phosphate groups to themselves. For instance
protein kinase A has 2 phosphorylation sites at positions Thr-197 and
Ser-338. But it is activated by binding of cAMP to the C-terminus. I
having trouble seeing the transistor analogy. Where and when is the voltage
applied to the kinase?
Mark:
As to memory, if an autophosphorylating kinases is conducting, then its
previous state was non-conducting.
Derek:
Again, I can't see what basis this transistor analogy has in actual biology.
'Conducting'? Kinases don't conduct. Kinases are very subtle enzymes which
can exhibit a whole spectrum of specificity and activity. They _aren't_
some kind of molecular flip-switch. If you want an analogy/metaphor to
electronics, then you'll need an analogue rather than a digital one. All
enzymes have Michaelis-Menten kinetics, they don't just flick on and off, so
when you say .....
"They can only be one or the other."
That really doesn't wash, at least not as far as a neurobiologist would be
concerned.
Mark:
One
might say that the cells doesn't know 'when' the previous state existed (1
msec ago? 10 seconds ago?), but there is still a piece of inferential data
available about the past which a signal processing system could use. Add a
stable electrical wave pattern to the system and much more can be made of
the inference.
Derek:
I have 2 problems with the above paragraph. Firstly, I still don't see what
your mechanism is for the cell 'knowing' its past states, and secondly I'm
not sure what 'Add a stable electrical wave pattern to the system' means.
It seems you want the cell to be rather like an electronic circuit. There
are too many soldering iron metaphors in here for a biologist to make sense
of the proposed mechanism.
Mark:
Since listening to neural signals crossing synapse membranes is very
difficult, most work on the role phosphorylating kinases comes from
observations of physiological change during embryonic neural
developments. They play key roles in neural differentiation, cell
migration and connectivity. Knock out a kinases and the brain doesn't
develop properly. For example, knocking out the gene for mDab1 (tyrosine
phosphorylated during embryonic development) in mice does nothing to change
the mice for the first week after birth. After that, they exhibit
increasing motor deficits and grossly malformed brains. Apparently, the
neural cells differentiate, but fail to migrate.
Derek:
Fair enough, but all this shows is that kinases have crucial roles to play
in the cell, and specifically in neurogenesis, and that there is a genetic
basis to both differentiation and migration.
Mark:
Edelman in 'Neural Darwinism' suggests neural systems develop according to
'neuronal group' selection. This provides a level of complexity left
'undetermined' by the genetic foundation. By binding Edelman's ideas to
Kock's, we get neuronal groups with binary signal processing at their
foundations (neural memetics).
Derek:
I still don't see how you make this leap. I grant you that neuronal
plasticity demonstrates that there is a lot to the brain which is not
genetic, but to go as far as to say .....
"The neural system is a self-determining organ, with its own developmental
memory founded upon its own mechanisms."
seems to be a tep too far. Your own example of the mDab1 knockout above
illustrates this. You say:
"Going back to the mouse example above, the observed lack of neural cell
migration shows cellular differentiation occurred (genetics) but not the
normal migration (neural memetics)."
The fact that the gene knockout inhibits the migration shows that the normal
migration _is_ genetically controlled. Even for those aspects of
neurogeneisis that are not genetically 'hard-wired', there is no evidence
that they can be influenced by cultural processes, and therefore no
justification for labelling them 'memetic'. Just because something isn't
rigidly genetically determined doesn't mean that it is therefore memetic.
Memetics, after all, whether one is an internalist or an externalist, is
about culturally transmitted somethings (mnemons/behaviours/information
delete as applicable). It isn't a bag into which everything non-genetic
falls.
Mark:
While you might object that migration of neural cells to proper locations
in the brain has little to do with cultural artifacts like Windsor knots,
the ability to create Windsor knots reflect physiological changes in the
brain of 'enabled' individuals, too. As an individual goes from 'blank' to
'Windsor knot' enabled psychological states, their brain changes, neural
cells extend themselves, connections are made. We are discussing a matter
of degree, not of kind.
Derek:
Of course, I don't disagree that learning must have some sort of effect on
the brain. What I'm saying is:
a) your attempt to explain it in terms of an electronics-type analogy
requires you to postulate things about kinases and/or other cellular
components which won't stand up to scrutiny by molecular biologists.
b) you still don't have a convincing mechanism for your hypothesised
'memory' effect
c) you are not justified in attaching the label 'memetic' to a process just
because it is not genetic. Besides, your gene knockout example above
actually argues the case for _greater_ genetic determination, not less.
Derek
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