Date: Wed, 22 Sep 1999 16:44:38 -0400
On Mon, 20 Sep 1999, John McCrone wrote:
First is the work by C. F. Stevens, which indicates that central
synapses
are not so digital as one would like to think. The on/off connectivity
used in many models is based on the best-studied synapse, the
neuromuscular junction. That connection has fail-safes, such that an
action potential is guaranteed to evoke transmitter release and
subsequent
muscle contraction. In contrast, Stevens' work with hippocampal
neurons
suggests strongly that in central connections, the probability of
transmitter release in response to an action potential is about 1 in 3.
There are ways to both increase and decrease this probability. Part of
the problem in discussing these mechanisms is that one has to think of
excitatory neruotransmitters passing on the electrical signal and also
modulatory neurotransmitters which can act on either the sending or
receiving neuron.
For example, assume an excitatory set of connections from neuron A, to
neuron B, and then to neuron C. Even assuming that one packet of
neurotransmitter secreted from A is sufficient to induce an action
potential in B, what is the probability of a single action potential in
A
resulting in a signal transmitted to C, given the probability of an
action
potential translating to transmitter secretion is 1 in 3 for both A and
B?
Simple probability says 1 in 9.
If at the junction between A and B there is another connection from
neuron
Y which enhances the probability of release (say via acetylcholine) to
1
in 2, the chances get better. However, there may also be a connection
from neuron Z onto B which decreases the probability of transmission
between B and C.
It's a mess.
It's a mess, especially considering that each of the hypothetical
neurons
A, B and C make significant numbers of excitatory input and output
connections with other cells, as well as having modulatory and
self-feedback contacts. Also, those modulatory connections at the
junctions of A and B or B and C do not apply to connections between A
and F
or B and D.
Although I tend to think on the "presynaptic release and post synaptic
receptor" scale of things, do remember that these processes produce the
spikes measured by people like Patricia Goldman-Rakic. This brings me
to
the second line of data pertinent to this discussion. Goldman-Rakic
records from single units in the prefrontal cortex of awake behaving
monkeys.
The behavior paradigm in her experiments is that of a delayed
response task. The stimulus is presented, then removed, and then at a
second cue the animal performs the appropriate response. She
has found cells where the firing pattern changes (either increases or
decreases, depending on the cell) at specific points in this paradigm
--
during the 'remembering stage', during the execution phase, etc.
Several
neurotransmitter types are involved in producing these correlated
spikes,
and she has also shown that the subtypes of transmitter receptor play
specific and separate roles in shaping the spike pattern.
John McCrone:
John McCrone:
Peter Main's connectionist machine, where "each node is continuously
responsive to its weighted inputs" is well worth considering, with the
addition that the weight of the inputs is dynamic rather than static.
The
weights in this case are the probabilities of release, of synaptic
transmission, which can be regulated by many different biochemical
pathways, pathways initiated by electrical activity or
neruotransmitters.
George Dawson:
I defend posting this discussion to the theoretical list because I
think
such details can inform theory, particularly when trying to integrate
neurochemistry with behavior. Ketamine was mentioned as disrupting
glutamate transmission, but it is crucial to the drug effect that there
are only certain types of glutamate receptors affected. These types
are
NMDA receptors, which in some cells seem to be responsible for
"coincidence detection." Mice overexpressing one NMDA subunit are
recently touted to be "smart" mice in spatial memory tasks. Heavy
recreational ketamine users report strong visual architectural
hallucinations. The first two concepts jibe -- increased coincidence
detection means faster learning -- but where does the second, the
altered
state of consciousness, fit in?
John Mikes pulled out the car analogy again, and I have to agree.
Locomotion is not in the tires, the engine, the axles or the gas tank,
yet
without everything in working order, the car doesn't move normally.
The
moving parts of the car are predictably dynamic, and perhaps the
plastic
connections in the brain will one day be understood. Still, once can't
understand a manual transmission without at least having the concept of
the gear in mind. I consider the details of neurotransmission to have
at least some utility in informing our attempts to understand the
brain.
Peg.
References:
Goldman-Rakic PS. Annals of the New York Academy of Sciences.
868:13-26,
1999 Apr 30.
Allen C. Stevens CF. An evaluation of causes for unreliability of
synaptic transmission. Proceedings of the National Academy of Sciences
of
the United States of America. 91(22):10380-3, 1994 Oct 25.
====
"The mental experience works well through the Internet,
From: "M. S. AtKisson"
Reply-To: "PSYCHE Discussion Forum (Theoretical emphasis)"
To: [email protected]
Subject: Re: neurochemistry of consciousness
Valerie, I too feel that once you have started to get some sort of
grip on
the "electrical circuit story" of how the brain is organised - the
easy to
see stuff of neuron spikes and neuron pathways - you have to then
weave in
the neurochemistry. The question is how to fit the neurochemistry
into an
"information processing" framework that is the standard way of
thinking
about what the brain does?
Although this is a theoretical list, I would like to point out two
areas
of molecular/physiological data that could inform this sort of
discussion.
George Dawson fairly neatly summed up part of the problem -- the
plethora
of specific transmitter receptor subtypes, the thousands of possible
combinations of transmitter and receptor 'pairs' at the synapse.
Still,
I believe the following is of use to people who like to think about
consciousness.
Most attempts to tie neurochemistry to consciousness suffer from the
fact
that people attempt to make the connection at too high a level.
Yes, and too globally. Many of the modulatory neurotransmitters do
have
'squishy' rather than point-to-point secretion profiles (norepinephrine
from the locus coeruleus terminals in the hippocampus is a prime
example),
but there is also specificity of connection.
It could be that the brain uses dopamine simply to turn a set of
prescribed
connections off and on - so in principle all transmitters are
functionally
equivalent and dopamine is used just to define a set of master
circuits
that can control a more general maze of circuitry.
I believe it is more complicated that this. Most people seem to regard
that there is a fixed set of circuits in the brain, and for certain
systems it is probably true -- the sorting of retinal input is a good
example. However, I believe the evidence is growing that there may be
at
least some 'circuits' which are created only as need arises.
There is practically no knowledge of the specifics of neuronal
pathways
(fiber counts, receptor counts, bandwidths, latencies) and arrays in humans
that would allow for basic estimates of information flow between anatomic sites
of interest.
Even with such information, the estimates are likely to be impossible.
Serial electron microscopy was used to reconstruct the connections
between
and among the few hundred neurons of the tiny worm C. elegans. This
labor
was in part intended to allow modelers to 'crack' the worm's entire
neural profile, giving architecture along with what is known about the
neurochemistry, but I don't think it was yet sufficient.
M. S. AtKisson
Department of Neuroscience, Tufts University
but the brain life is blocked off by neurodynamics,
which is God's own firewall preventing philosophers
from accessing brain codes. The way of the hacker is hard."
Walter J. Freeman