View Full Version : "Projections from the PAG to the ventral tegmental area (VTA) suggest.."

10-20-14, 10:32 PM
I am not familiar with the researchers or the research methods below?

I am wondering if some opiates (?) promote the development of dopamine receptors(?), early in life?

So I am posting it here for discussion and learning purposes, please leave room for error in my interpretation/question of the OP research.

Insights appreciated.


The midbrain central gray (periaqueductal gray; PAG) mediates defensive behaviors and is implicated in the rewarding effects of opiate drugs. Projections from the PAG to the ventral tegmental area (VTA) suggest that this region might also regulate behaviors involving motivation and cognition. However, studies have not yet examined the morphological features of PAG axons in the VTA or whether they synapse onto dopamine (DA) or GABA neurons. In this study, we injected anterograde tracers into the rat PAG and used immunoperoxidase to visualize the projections to the VTA. Immunogold-silver labeling for tyrosine hydroxylase (TH) or GABA was then used to identify the phenotype of innervated cells. Electron microscopic examination of the VTA revealed axons labeled anterogradely from the PAG, including myelinated and unmyelinated fibers and axon varicosities, some of which formed identifiable synapses. Approximately 55% of these synaptic contacts were of the symmetric (presumably inhibitory) type; the rest were asymmetric (presumably excitatory). These findings are consistent with the presence of both GABA and glutamate projection neurons in the PAG. Some PAG axons contained dense-cored vesicles indicating the presence of neuropeptides in addition to classical neurotransmitters. PAG projections synapsed onto both DA and GABA cells with no obvious selectivity, providing the first anatomical evidence for these direct connections. The results suggest a diverse nature of PAG physiological actions on midbrain neurons. Moreover, as both the VTA and PAG are implicated in the reinforcing actions of opiates, our findings provide a potential substrate for some of the rewarding effects of these drugs.

Keywords: opiates, periaqueductal gray, reward, tract-tracing, ultrastructure

Periaqueductal Gray Afferents Synapse onto Dopamine and GABA Neurons In the Rat Ventral Tegmental Area (


10-21-14, 01:38 PM
Is that a mechanism for pain (PAG) driving aversion (the opposite of dopaminergic system activation) ?

10-21-14, 01:49 PM
explain it to me like im 5.

10-21-14, 08:59 PM
In the human infant, the growth of dopamine-rich nerve terminals and the development of dopamine receptors is stimulated by chemicals released in the brain during the experience of joy, the ecstatic joy that comes from the perfectly attuned mother-child mutual gaze interaction.

Happy interactions between mother and infant generate motivation and arousal by activating cells in the midbrain that release endorphins, thereby inducing in the infant a joyful, exhilarating state.

They also trigger the release of dopamine.

Both endorphins and dopamine promote the development of new connections in the prefrontal cortex.

Dopamine released from the midbrain also triggers the growth of nerve cells and blood vessels in the right prefrontal cortex and promotes the growth of dopamine receptors.

A relative scarcity of such receptors and blood supply is thought to be one of the major physiological dimensions of ADD.

Gabor Mate M.D., "Scattered", Chapter: The Footprints Of Infancy, P 83.


10-21-14, 09:41 PM
..We know that in situations of fear in which the brain chooses the running options rather than freezing, the brain stem disengages part of the pain-transmission circuitry--a bit like pulling the phone plug.

The periaqueductal gray, which controls these responses, can also command the secretion of natural opioids and achieve precisely what taking an analgesic would achieve: elimination of pain signals.

Antonio Damasio, "SELF comes to MIND", Constructing The Conscious Brain, Chapter: Emotions and Feelings, P129.


10-22-14, 05:54 AM
So the point'd be to try and identify whenever the individual (from conception onwards) is in distress and to avoid that environmental stressor from recurring.

We know that separation distress occurs in child so we need to prevent it from happening.

So - the point being that normal development can be assessed by avoiding all clear distressors and if the environment is set for this lifestyle to be led - that the child will develop appropriately ?

It's clear that throwing mother back into the workplace after giving birth isn't a good thing for child or mother.
Peripheral has provided evidence in previous threads that the need for mother by child seems to wane as the child grows older (to fade at 7 yrs ... ... I think ?)

- but the point that I'm going to stick with is that we don't need to worry about all of these very important issues if we remove compulsion from life by eliminating the NEED to do something immoral (all things for money are immoral) in order to survive.

Recent publication - increased asthma in people who are in insecure jobs.

No matter what medical research you do - there's no way you'll find a drug which stops you from feeling job insecurity.

The only solution is to eliminate the need for a job for survival - and eveything else'll fall into place.

10-22-14, 08:09 AM
'dopamine' - seeking attachment ?
'endorphin' - attached ?

Attachment to mate ?
Attachment to child ?
Attachment between all members in a species ?

What is empathy ?
Must represent attachment between all members in a species.
Human beings generally feel bad when others suffer.

So ... ... ... ADHD as the process of social species formation (attachment) ? or rather the underlying condition which isn't allowed to express itself in a fundamentally immoral society results in disorder

- representing (in effect) something like the equivalent of a child not being able to attach to a mother.

An individual not being able to attach to a species.

ADHD as an enforcedly social individual that cannot gain attachment (satisfaction) in a society which prevents attachment through hierarchy formation.

Stuck in D/NE requirement (the ADHD meds) and unable to take it to the next level - Oxytocin/Vasopressin/Endorphin release because the process of attachment formation is prevented by (anti-)social rules which people are required to adhere to.

10-22-14, 08:21 AM
So - the logical conclusion to that idea is that we're forming an actual evolutionary flat structure which parallels the current trend toward global anarchy-based governance structure and voluntaryism.

ie under the cover - a new species which is engineered to operate within a flat structure - of equals.

Reward system - collaborative quality.

Educational system - towards wisdom.

Upon attaining wisdom - {{{whatever}}} - you're free.

10-22-14, 08:39 AM
So to 'love thy neighbour' simply means to attach (dopamine -> endorphin) and then to live with presumably

parental attachment
parental-child attachment
individual attachment occurring in that order

Failure 'attaching' -> attachment requires D/NE administration ie adder drugs or self-medication.

10-22-14, 09:59 AM
Because TSA is a histone deacetylase inhibitor, the researchers speculated that, upon its injection, the resulting histone acetylation and increased gene expression would affect partner preference in the prairie voles. And, in fact, this was true. The voles that received the histone-modifying drug formed exclusive pair-bonds even though they only interacted for 6 hours and weren’t allowed to mate!

carbs -> polygamy
ketosis -> monogamy / pair-bonding across the board ... ...

10-22-14, 10:02 AM
So metabolism again ... ... ...

Western society - diseases of excess carb consumption (see Ratey/Kunga Dorji).
Excess carb (and fat consumption) driven by distress (see rat park + observation that opiate inhibitors inhibit desire for sweet fatty food)
Ketosis state associates with neural complexity, health, pair-bond formation
- simply just a trigger:
carbs - growth/proliferation
ketosis - rearrangement (neural) and anti-growth anti-proliferation

So basically
[1] No distress
[2] Appetite regulation - fine
[3] Not fat/carbs but ketosis
[4] Happy ketosis - and physiological [not pathophysiological] state retained

Everything from healthy body, mind, spirit ensured given a moral society with wisdom education arranged.

10-22-14, 10:08 AM

If you're looking for love - travel with a lovely lady on a 7 day fast and then live happily ever after.

10-23-14, 07:29 AM
The basis to quality (building personal quality) - highly interconnected microcircuit formation (wherever) we 'train' ouselves.

In this review, which is part of the TINS Microcircuits Special Feature, we compare the connectivity designs in spinal, hippocampal, neocortical and cerebellar microcircuits, and discuss the different computational challenges that each microcircuit faces.


HDAC inhibitors assist the process of microcircuit formation - the state of ketosis.

Evolutionarily - survival challenged (going into ketosis) requires the individual to be at the top of their game ie construct high quality perceptual / sensory machinery ie to hear threats and to see food off in the distance ... ...

So from fasting/ketosis to improved personal quality through requiring it to survive - so the basic paradigm has been retained as the 'quality' of experience rather than the quality of perception for survival reasons has become our new prime directive.

To experience quality through training and assisting learning through ketosis.


Has to be admitted that the carb -> fat switch with respect to growth (body) -> rearrangement (to complexity of neural structures) is REALLY neat - probably favourite idea of the lot ... ... which means that it's highly explanatory.


At its core it's a carb vs fat battle - with the ketone body formed from duality of carb/fat ie 'hitting the wall' with a little fat on us - which triumphs as the quality (microcircuit formation) permissive energetic substrate for the body, brain and mind.


Definitely correct.

10-23-14, 07:42 AM

Brain food is no food in a relaxed environment.

Optimally highly interconnected micro-circuit formation - higher personal quality.

10-23-14, 07:53 AM
It means that greedy world ie people shovling fat/carbs down their cakeholes 'll be as of low quality as can be.

Reference to the vast majority of people being vogon bureaucratic poets coming out with rule after rule which NOBODY can follow (cough lawyer vogons cough).

Can't delegate fasting, exercise, eating your veg, cold exposure ... ... ... <- mitochondrial biogenesis whilst they're chomping away on lovely tasty ketone bodies.

10-23-14, 08:05 AM
Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy.

The answer is easy.

Approaching GAME OVER.

Growth - carbs
Quality - ketones -> epigenetic remodelling downregulating growth/proliferation and upregulating interconnections within neural microcircuits underlying quality in whichever domain one chooses to 'train' oneself in.

Question - what can molecular biology tell us about nerve/brain/mind functioning ?
Answer - it opens the door to the closure of one basic paradigm (growth) and to the start of another ... ... though how we 'develop' quality is based on whichever avenue we attempt to better ourselves in.

10-23-14, 08:08 AM
Endocrine metabiochemical epidemiological reasoning takes out and soundly beats Neurogenetic Immuno-oncological bioinformatics.


Cambridge wins the b.o race.

10-23-14, 10:53 AM
The neocortical microcircuit as a tabula rasa.

Environment (practice,learn,train), Environment (lack of distress), Environment (biochemical- ketosis) basis to the individual developing personal quality.

We live in a world where we train in pointless things, are chronically distressed and live for blood glucose elevation.

These data also indicate that the local neocortical microcircuit has the potential to be differently rewired (

10-23-14, 03:30 PM
Focusing on the more implicit affective stage of early development, before the age of 4*.

Healthy blood flow to the higher prefrontal cortex when Infant experiences comfortable (balanced) emotional environment. (perceived or real)

Unhealthy blood flow away from the prefrontal cortex when Infant experiences chronic uncomfortable (unbalanced) emotional environment. (perceived or real)