A Theory of Neuropeptides?

Peter F. effectivespamblock at ozemail.com.au
Wed Jan 7 10:10:10 EST 2004

You are not wrong!

It is in *every way* plausible (i.e., not just because it has been
evidenced) that some *key* type glutaminergic neurons ("key" in respect of
what I am about to suggest - or perhaps rather assert and conclude), *can*
to release substance-P at a 'certain' treshold of excitatory (at least
potentially directly distress, or flight, motivating) firing, AND at some
still higher frequency (or same frequency but longer duration?) some opioid
type neuromodulator.

By combining our (incomplete) knowledge of how our brains and bodies work in
healthy, harmed and/or harrassed, and hypnotized humans (and in case
of/relation to corresponding psychologies, patterns of behaviour, and
somatic, and peripheral nervous system, functioning - including the role
played in human cognitive, affective, and visceromotor levels of
consciousness by opioid (and other) neuromodulators and their receptors)
with an "evolutionary psychology type" analysis and strategic philosophical
categorization - logically leading to a recognition that opioid secretion
stimulating life-situations (categorized as a subtype of "adversity type"
evolutionary pressures) often overlap (in phylogenetic time and space)
with different "*constructively* naturally selective" backgrounds consisting
of "Opportunity" (~=at least complexity maintaining but on the whole
type evolutionary pressures, and to finish-off with, a sEPTic humor
requiring counter-phobic contemplation of the by me attached largely
metaphorical map of how brains work (see below), one can concEPTualize
(given a no more than necessary poetic freedom) an immensely unifying
insight (one that also imply and reflect a certain 'natural irony') into our
"AEVASIVE" [derived from: "ambi-advantageously" evolved, vitally actention
selecting, system - incorporating various endoopiates"] mental and
behavioural and brain functional characteristics.

These remaining, likewise SEPTIC (i.e. based on by Science established
principles, theories, interpretations & concepts), "map"-plotting, mainly
ingredients of the corresponding part of
my explanatory philosophical take on What Is going on, are as follows:

Slowly as well as rapidly traumatic situations occur - as a result of
environmental (or internal) "absences" (features of an individual's
environment that chronically deprive some not vitally essential but
nevertheless causing painful distress motivating intensities of firing by
correspondingly feature-detecting neurons) as well as "presences".

Central need-fulfillment serving by being rapidly life-situation assessing
neurons, brought on-line through the process of ontogeny, rapidly give
*"preliminary"* (as in, "preparatory of consciousness") expression to both
"endogenous information" (reflecting, via the DNA-code, naturally
selective/evolutionary, hence in a sense also
*life-situational* (in consideration of all the lives individually lived
ancestral populations) pressures, AND exogenous (environmental), information
that they receive, rapidly relay/process, and store.

These fast and phasic "specific type" neurons provide a behavior
selecting/motivating INPUT to central "reticular activating" and
"nonspecific" type of neurons -- i.e. neurons of the "diffuse modulatory
system", corresponding to nuclei located in several regions of the brainstem
reticular formation - including the diffuse thalamic 'nuclei';

Neurons of the latter type do, in an neuropsychophysiological sense,
"essentially energize" [all contents + qualities (~"levels") + intensities
of] what may be collectively referred to as Consiousness;

The human (and animal) nervous system "consists" of "actention modules"
["actention" is an amalgam of "attention" (by conventional association
mainly mental) and action (conversely mainly motor or muscle effected)].

It is fun to consider that actention modules (or "program structures")
together form an individual's actention selection system (ASS). ;-)

In Discovery Magazine I saw a super-crude and turgid metaphorical picture of
the ASS. It looked like a few bunched-together stems bifurcating into a
'stalk-like' (more complex the higher up the towards the top of each
'stalk') boquet of modular programs structures subserving (from mainly
mental to, mainly muscle-effected, or motor type) "focuses of actention".

Actention modules can be seen to be in mutual competition as far as (at the
level at which) they are
functionally incompatible.

A single (relatively or simple - as opposed to complex) actention module may
compete in a "low division" whilst being part of a "team". A "team" is a
metaphor (within the metaphor) for a complex actention module at a high
division of the overall {Olympic sized} competition.
All "teams" have as a funding (fundamental) member at least a few actention
modules that are
independently simultaneously actively competing within a "lower, single
player sport,

Within any discipline of the overall Olympic-sized competition each
actention modular team or competitor is "weighted".

The "weighting" is done by genetic/phylogenetic inheritance
(phylogenetically significant life-situational adversity and opportunity),
by past (stored in longterm memory), and by just prior (stored in short-term
memory) environmental influences. However the continuous outcome of the
competition (within the actention selection system) is importantly also
determined by the concurrent actention selection affecting (cheering and/or
by direct sensory/environmental input/features/conditions (AKA "the olympic
games audience");

The "prize" being competed for is transient dominance (or becoming a
"dominant" (a Russian reference to this concept is available)) within the
(thus) dynamically modular brain, or nervous system, or
(as a fresh and encompassing EPT alternative) "Actention Selection System"

The prize ('awarded to' actention modules) come in the form of being allowed
to be briefly allowed to step-up/emerge as a (from) mainly mental to mainly
visceromotor "_focuse_ of actention"; and/or as part of a thus as if
temporarily winning "team", formed from a broad (hierarchically organized)
mixture of mental AND visceromotor actention modules.

Mind you, within the "simple disciplines=basic and heavy weight-divisions"
there is not much of a competition - e.g., the basic actention module
responsible for breathing is only sporadically competed with by the few the
modules that are respectively responsible for holding one's breath,
coughing, and hiccuping.]

That the universal tool used within the competition is mutual ("lateral")
inhibition - or "center/surround excitation/inhibition".

Perhaps soon, you too will understand what I know about our AEVASIVE origing
and nature. %-)



Here is a de facto outline of locations, fiber projection, and chemical
profile, of "RAT neurons" that I stole from the Net:

Lecture 17: Reticular Activating System and Neuromodulation

Reading: Bear, Connors and Paradiso, chapter 15, pgs 419-426

Purves et al. chapter 6, pgs 112-115

chapter 7, pgs 138-141

Reticular Activating System - This system (also referred to as a diffuse
modulatory system) consists of a collection of nuclei located in several
regions of the brainstem and ventral telencephalon. It is intimately
involved in the regulation of the sleep-waking cycle, arousal, and
attention. Disruption of one or more components of the system can lead to
loss of consciousness and coma. Overactivation of the system can lead to
hyperactivity, hypervigilance and anxiety. Similarly, disturbances of the
system can lead to a variety of psychiatric disorders.

There are four principal sets of nuclei that act as diffuse modulatory
systems. They are each composed of one or more nuclei consisting of small
populations of neurons that send widespread projections to large regions of
the central nervous system. Each system utilizes a distinct neurotransmitter

The Locus Coeruleus (Norepinephrine, NE) - This structure is located in the
Pons, and consists of a small population of neurons that send broadly
divergent projections to nearly every portion of the central nervous system.
It uses Norepinephrine as a neurotransmitter. The cells in this structure
are activated by novel sensory stimuli and remain highly active during
states of arousal. NE is involved in regulating states of arousal and
attentiveness. Overactivity of this system can lead to hypervigilance and
anxiety disorders. Hypoactivity in this system can contribute to depression
(Fig. 15-11 in Bear et al.).

Receptor Subtypes

Alpha (a )1,2

Beta (b )1,2

The Raphe Nuclei (Serotonin, 5-HT) - This is a collection of nuclei
distributed throughout the brainstem in the midbrain, Pons and medulla. They
project widely throughout most of the central nervous system. The rostral
nuclei project to the cerebral cortex and thalamus, while the more caudal
nuclei project to the cerebellum and spinal cord. The neurons in the rostral
structures are active during the waking state, and quite during sleep. The
cells in the Raphe nuclei use Serotonin as a neurotransmitter. The chemical
name for Serotonin is 5-hydroxytryptamine and it is often referred to as
5-HT for short. Hypoactivity in this system is thought to play a major role
in depression (Fig. 15-12 in Bear et al.).

Receptor Subtypes

5-HT1 - 5-HT5

The Ventral Tegmental Area (Dopamine, DA) - This is a collection of nuclei
located in the ventral regions of the midbrain. They send widespread
projections to the frontal regions of the cerebral cortex (mesocortical),
and to most of the structures in the limbic system (mesolimbic). The cells
in these nuclei use Dopamine as a neurotransmitter. These systems are
thought to contribute to cognitive function by modulating frontal cortical
activity, and to contribute to the reinforcement of certain behaviors by
mediating pleasurable sensations. They have been implicated in the
mechanisms underlying schizophrenia and drug addiction (Fig. 15-13 in Bear
et al.).

Receptor Subtypes

D1 - D5

The Cholinergic Basal Forebrain and Brainstem Nuclei (Acetylcholine, ACh) -
This is a collection of nuclei located in the ventral regions of the
telencephalon, and in the rostral end of the Pons. They project to large
regions of the central nervous system including the telencephalon,
diencephalon and limbic system. The cells in these structures are active
during states of arousal and are thought to contribute to the level of
behavioral vigilance. They use Acetylcholine as a neurotransmitter. The
cholinergic nuclei are also thought to contribute to synaptic plasticity and
therefore be involved in the mechanisms that enable learning and memory to
take place. Disruption of the cholinergic system is thought to contribute to
the memory deficits of disorders such as Alzheimer's disease (Fig. 15-14 in
Bear et al.).

Receptor Subtypes



M1 - M5

Neuromodulation - The neurotransmitters in each of the diffuse systems are
referred to as neuromodulators. The postsynaptic actions of these chemicals
are slow, long-lasting, and act by changing the excitability of the cells
via second messenger systems. They can act through multiple postsynaptic and
presynaptic receptor subtypes to produce a variety of actions on transmitter
release and postsynaptic excitability.

The Biogenic Amines

This is a class of five compounds that function as neuromodulators. They
consist of the catecholamines (dopamine, norepinephrine and epinephrine),
and histamine and serotonin.

The catecholamines are generated from a common biosynthetic pathway (Fig.
6-10). The amino acid tyrosine serves as the precursor to the synthetic
pathway. This compound is converted to dihydroxyphenylalanine (Dopa) by the
enzyme tyrosine hydroxylase. Dopa is converted to Dopamine by the enzyme
Dopa-decarboxylase. Dopamine is converted to Norepinephrine by
Dopamine-beta-hydroxylase, and Norepinephrine is converted to Epinephrine by


The amino acid Tryptophan serves as the precursor for Serotonin
(5-hydroxytryptamine, 5-HT). Tryptophan is converted to 5-hydroxytryptophan
by the enzyme tryptophan-hydroxylase. 5-hydroxytryptophan is converted to
serotonin by the enzyme aromatic-amino-acid-decarboxylase (Fig. 6-11).


Acetylcholine, which falls under its own chemical classification, is
synthesized from the compounds choline and acetyl-CoA by the enzyme

Neuromodulatory Actions

Neuromodulators act both presynaptically and postsynaptically by binding to
metabotropic receptors that utilize G-proteins to carry out inhibitory or
excitatory actions. The G-proteins can either act directly on an ion channel
or indirectly by initiating the synthesis of a second messenger (Fig. 7-10).

G-Proteins (Guanine nucleotide binding proteins)

They consist of three subunits, alpha, beta and gamma. They also fall into
two general classes, stimulatory (Gs) and inhibitory (Gi).

1) In the resting state, GDP is bound to the alpha subunit.

2) When neurotransmitter binds to the receptor protein, the G-protein
exchanges GDP for GTP.

3) The now activated G-protein splits into two parts: the alpha subunit
bound to GTP, and the beta-gamma complex.

4) Both component G-proteins can act as effectors by acting directly on ion
channels or by influencing the production of 2nd messengers.

Direct actions - when activated, the G-protein can act on an ion channel to
either increase or decrease its conductance. This process is relatively fast
and takes 10s of milliseconds to initiate.

Indirect actions - when activated, the G-protein can act on enzymes to
either stimulate or suppress the synthesis of a 2nd messenger. 2nd
messengers act on specific enzymes to stimulate or inhibit their activity.
They often influence the activity of protein kinases and phosphatases which
act by phosphorylating and dephosphorylating proteins, respectively. The
state of phophorylation of an ion channel can regulate its conductance and
thus the excitability of a cell.

5) The alpha subunit can hydrolyze GTP and convert itself back to the
inactive form that is bound to the beta-gamma complex.

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