Neuron / neurotransmitter selection question

Kenneth Collins k.p.collins at worldnet.att.net_NOSPAM
Thu Feb 27 06:16:06 EST 2003

Hi John.

"John H." <johnh at faraway.xxx> wrote in message
news:ZPj7a.243$6r2.6767 at nnrp1.ozemail.com.au...
| Last year I did read some research to the effect that
administration of BDNF
| switched a cardiac neuron from excitatory to inhibitory function in
under 15
| minutes. Sounds weird I know and have no idea about how it could
work. If
| you like will try to find the reference in my archives. No, here it
| 04/07/02 6:50
| Nature Neuroscience
| Published online: 6 May 2002, doi:10.1038/nn853
| June 2002 Volume 5 Number 6 pp 539 - 545
| A rapid switch in sympathetic neurotransmitter release properties
| by the p75 receptor
| Bo Yang1, 2, John D. Slonimsky1, 2 & Susan J. Birren1
| 1. Department of Biology, Volen Center for Complex Systems, 415
South St.,
| M/S 008, Brandeis University, Waltham, Massachusetts 02454, USA
| 2. The first two authors contributed equally to this work.
| Correspondence should be addressed to S J Birren. (e-mail:
| (/neuro/email_response/email.taf?address=birren%40brandeis.edu))
| Cardiac function is modulated by norepinephrine release from
| sympathetic neurons. These neurons also form excitatory connections
| cardiac myocytes in culture. Here we report that brain-derived
| factor (BDNF) altered the neurotransmitter release properties of
| sympathetic neuron-myocyte connections in rodent cell culture,
leading to a
| rapid shift from excitatory to inhibitory cholinergic transmission
| response to neuronal stimulation. Fifteen minutes of BDNF perfusion
| sufficient to cause this shift to inhibitory transmission,
indicating that
| BDNF promotes preferential release of acetylcholine in response to
| stimulation. We found that p75-/- neurons did not release
acetylcholine in
| response to BDNF and that neurons overexpressing p75 showed
| cholinergic transmission, indicating that the actions of BDNF are
| through the p75 neurotrophin receptor. Our findings indicate that
p75 is
| involved in modulating the release of distinct neurotransmitter
| resulting in a functional switch between excitatory and inhibitory
| neurotransmission in individual neurons
| --
| [...]

The problem that seems intractable when one focuses upon individual
neurons becomes easy when it's set in the context of
whole-nervous-system functionality. If an E -> I transformation, such
as the one that you've cited, were not compensated for, elsewhere
within the global neural architecture, the global system's
'functioning' would build to a wildly-uncontrolled 'explosion' of
neural activation. Since this doesn't happen [except in
organically-'damaged' conditions such as epillepsy, etc.] it's easy
to see that every dynamic such as the one under consideration must be
compensated-for elsewhere in the global neural architecture.

In this way, and for the same reason, it's also easy to see that what
nervous systems do is converge upon global TD E/I-minimized
activation 'states'. That is, the =only= way wildly-uncontrolled
activation 'states' can be avoided is if global nervous system
function is, in fact, rigorously ordered in ways that have been
expressly 'engineered' by evolutionary dynamics to converge upon TD

Although the problem is 'intractable' when it's considered at the
'level' of all individual neurons taken-together, it's just easy when
it's addressed at the level of global nervous system function. Since
this can be stated rigorously, it follows that this governing
principle can then be used to analyze global nervous system
functionality all the way down to the 'level' of ionic conductances
within individual neurons. In this approach, one starts at the global
'level', and works down to the microscopic 'level', at each 'step',
identifying the TD E/I-convergence 'hand-shaking'. Many examples of
this sort of analysis are given in AoK, the major ones being noted
with a phrase like "this is an example of dynamics which, over the
short term, contradict the fundamental wisdom of nervous system
function that TD E/I must be minimized". Particular examples are with
respect to "reticular system" functioning [AoK, Ap3, 4, 5, 7] and
with respect to the "meta-" 'states' {AoK, Ap7 & 8].

One can also see the macroscopic underpinning nervous system dynamics
in examples such as the "infant's crying behaviro" of AoK, Ap5. One
can see the relatively-stochastice behavioral dynamics, acting at a
distance to induce TD E/I(up) within Parents' nervous systems, the TD
E/I-minimization within the adult nervous systems which is evidenced
in their converging upon behaviors that will provide nurturance to
the, say, 'hungry' Infant, which, then, 'shuts-down' the Infant's
manifestation of relatively-stochastice behavioral by-production,
which eliminates the TD E/I(up) that the Infant's crying behavior
induced within the parental nervous systems.

One can easily see that it is global TD E/I-minimization that governs
all of this beautifully-functional stuff.

It was through such analyses, undertaken via as many approaches,
simultaneously, as I could think-up, that NDT was developed.

At first, I was so 'pissed-off' with the "stupidly-simple'
"energy-consumption minimization" [TD E/I-minimization] principle,
that I worked tirelessly to 'break' it, only to see it grow stronger
the deeper I looked in my efforts to 'break' it, until, finially, I
was totally 'humbled' by it's awesome, and Truly-Beautiful
functionality. It had won me over.

This was a real 'fight'. I through myself into it with complete
devotion, ransacking the Neuroscience stacks as they then existed,
looking for anything that would 'break' the TD E/I-minimization
principle. After more than 9 years, I'd found nothing. In the
meanwhile, I'd learned robustly about the TD E/I-minimization
principle - where, how, and why it exists everywhere within the
neural architecture.

AoK is a a brief overview of my findings.

Cheers, John, ken

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