Timing is key in the proper wiring of the brain: study

December 19, 2011, Yale University

(Medical Xpress) -- After birth, the developing brain is largely shaped by experiences in the environment. However, neurobiologists at Yale and elsewhere have also shown that for many functions the successful wiring of neural circuits depends upon spontaneous activity in the brain that arises before birth independent of external influences.

Now Yale researchers have shown in research published online Dec. 18 in the journal that the timing of this activity is crucial to the development of vision — and perhaps to other key neural processes that have been implicated in autism and other neurodevelopmental disorders.

“This spontaneous activity is not dependent upon external sensory stimuli,” said Michael Crair, the William Ziegler III Associate Professor of Neurobiology and associate professor of ophthalmology and visual science and senior author of the paper. “We want to know where this activity comes from and how does it work.”

Yale researchers tried to interfere with this spontaneous activity in neonatal mice through a technique called optogenetics – or the manipulation of cells genetically engineered to be activated by light. The Yale team showed that proper wiring of connections between the eye and brain depended upon exactly when this spontaneous activity occurs. When the researchers simultaneously induced retinal activity in both eyes of a neonatal mouse, they found the visual connections did not develop properly. However, when they induced activity first in one eye and then the other, neural connections were unaffected or even enhanced.

Crair said that rhythmic spontaneous activity has been implicated in proper development of many brain areas, including the cortex, cerebellum, and spinal cord. He said it is possible that a disruption in the timing of this spontaneous activity could play a role in a host of developmental disorders.

“The genes thought to be involved in autism involve the formation and function of brain synapses and , and that is exactly what is getting messed up when we interfere with brain activity early in development,” Crair said.

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2.3 / 5 (9) Dec 19, 2011
Excellent. Another step in the war against Republican disease.
1.9 / 5 (9) Dec 19, 2011
Another unsolvable conundrum for evolutionists - besides the already perplexing one of why there's a baby in the first place[ where and how did sex "evolve"?].
The myriad [irreducibly] complex issues involved in creating another human being in the mother's womb should by now have flattened any arguments in favor of step-wise evolution, however the materialistic philosophical requirements outweigh any commonsense whatsoever.
5 / 5 (1) Dec 19, 2011
Another unsolvable conundrum for evolutionists - besides the already perplexing one of why there's a baby in the first place

Ask your parents about the birds and the bees.
[ where and how did sex "evolve"?]

The same way as everything else. Long ago, gradually.
The myriad [irreducibly] complex issues involved in creating another human being in the mother's womb should by now have flattened any arguments in favor of step-wise evolution, however the materialistic philosophical requirements outweigh any commonsense whatsoever.

No, ID and Michael Behe's irreducible complexity have been flattened, more times than I care to count. If you follow the link, there is a list of published papers that put the lie to your claims.
2.3 / 5 (3) Dec 19, 2011
Excellent. Another step in the war against Republican disease.

Oh look, another completely irrelevant Vendicar post.
1 / 5 (1) Dec 19, 2011
Excellent article. I asserted 'sentience' loses all conventional psychological meaning during gestation long ago:
This spontaneous activity is not dependent upon external sensory stimuli - Michael Crair

We want to know where this activity comes from and how does it work. - Michael Crair

This activity is below threshold 'noise'(cell's own activity).
And it works - as far as timing (exceeding threshold) is concern - as a biochemical Kalman filter.

"Functioning senses" in the sense that the senses are so underdeveloped as not able to perform the intended future function during gestation is irrelevant. The brain still receives signals from 'non-functioning' senses not able to perform their pre-dispositional function. Critical to neuronal and brain development in establishing mutually exchanging pathways before post birth.

5 / 5 (1) Dec 19, 2011
The mammalian placenta allows in utero chemical communication that appears to prepare the infant for experiences with food odors and social odors in the postnatal period. Social odors are causally indicated in the infant-mother bond that probably is facilitated by association with the mother's lactation and infant's nutrition associated with hormones and brain development.

Lynch et al (2011)"Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in [placental] mammals, indicates that a process of stepwise evolution, which appears to have recruited 1532 genes and the interactions among them is unlikely. Saying no stepwise evolution suggests a systematic force that has not yet been detailed; one that might explain the concurrent evolution of interactions among 1532 genes. There are some other probability calculations that may be pertinent also.
1 / 5 (1) Dec 20, 2011
Hmmm...simplify. At least for starters and start with the Hox genes.


Vincent J. Lynch "The birth of the uterus: genes that help determine what goes right or wrong in pregnancy also enabled early mammals to switch from laying eggs to bearing live young".


Enjoy. A truly fascinating tale of research to which JVK's link and mine shows where this researcher is headed. And forgive us for digressing. Since 2005, obviously the researcher has spotted 1532 'participants' under Hox 'orchestration' to which he labels "unlikely". He is open to an idea of a "systematic force" when tossing aside a stepwise evolution. I guess positive selection fell short.

Extra thanks from me to JVK for pointing towards an extraordinary researcher and his team.

And put this to the test. Can fetuses smell and/or taste?(Amniotic fluids)

What about adults submerged in water? Can they smell the water they can obviously taste?

5 / 5 (1) Dec 20, 2011
Another reason I remain open to the idea of a "systematic force" it that there seems to be no explanation for the "Accelerated Recruitment of New Brain Development Genes into the Human Genome" http://www.physor...ain.html or for the evolution of sexual reproduction in yeasts http://stke.scien...186/ra54
While the number of groups reporting on de novo genes is currently minimal, the fact that these novel genes can be found in species from yeasts to mammals may make it worthwhile for others to take a second look at the concept of stepwise evolution.
And, yes, the in utero ability of mammals to detect chemicals in amniotic fluid has been demonstrated in work by Julie Mennella et al. (and others, I think).
1 / 5 (3) Dec 20, 2011
"Oh look, another completely irrelevant Vendicar post."

1 / 5 (1) Dec 20, 2011
Thks again for the further reading links:

"Prenatal and Postnatal Flavor Learning by Human Infants" - Julie Mennella et al"

Here a few excerpts:
"During the past few decades, a series of experiments demonstrated that fetal learning does indeed occur."

"The fetus not only learns the speech characteristics of the mother prenatally,..."

Chomsky never considered a prenatal 'classroom' like this for language acquisition and/or sound recognition.

Sound itself has 'innate' or intrinsic properties. There is no reason that these properties of sound can not imprint or even structure the target (the fetus till birth) prenatally.
This, for me, is the "systematic force" for the origin of all human language.

Now the border between "external sensory stimuli" and "prenatal sensory experiences" can be reasonably questioned.

This thread's digression excursion has been most impressive for me.
not rated yet Dec 20, 2011
Chomsky, to his defense, did consider an innate biological structure. The prerequisite for life's (innate?)adaptation is, in any case, physical in origin.
5 / 5 (1) Dec 20, 2011
Yes, from the perspective of evolutionary biology, there must be both genetically predisposed brain structures and those that also are either activated, or not, by sensory input from the environment. The mammalian placenta blurs distinctions, or "borders" between genetic predisposition and effects of either the molar or molecular environment, prenatally or postnatally. I co-authored a 1996 paper that helped to explain how the molar and molecular are involved in the development of sexual preferences.
I have since followed with additional published works on the same theme. Evidence from molecular biologists that further blurs the distinctions others make in discussions of prenatal and postnatal development seems poised to bring together data from different disciplines that further addresses the influence of timing on the wiring of the brain and of developmental disorders.
not rated yet Dec 20, 2011
"Oh look, another completely irrelevant Vendicar post."


I shouldn't even dignify you with a response.


Look at me! My name is Vendicar Decarian and I make unnecessary quips towards republicans all the time because I think they're witty!

and I don't even really like republicans.
2.3 / 5 (3) Dec 20, 2011
"Look at me! My name is Vendicar Decarian and I make unnecessary quips towards republicans all the time because I think they're witty!"

They certainly keep me amused. Well done Vendicar.

not rated yet Dec 21, 2011
Thks for the link to the essay in dedication. The nondisclosure clauses for research are a burden to collaboration. It impedes progress.
not rated yet Dec 21, 2011
You're welcome. I'm an independent researcher and have always disclosed whatever information is required to further the understanding of the basic principles of biology and levels of biological organization. Some of my antagonists complain about my commercial involvement with pheromones, but I've maintained my scientific credibility quite well. Meanwhile, too few people understand the reason for focus on how sensory input can be directly linked via gene activation to behavior. Brain development is primarily a function of olfactory/pheromonal input, and this can be tracked back to microbes. Somehow, people still think they are more visual creatures, probably because they do not understand the biology of classically conditioned responses.
not rated yet Dec 22, 2011
This is my focus:

And when I read this:
"...The researchers found that typical brain processing of auditory rhythms associated with phonemes was disrupted in the left auditory cortex of dyslexics and that this deficit correlated with measures of speech sound processing..."

I find myself wishing the researchers had sought a correlation measure between the brain's distribution of brain specific estrogen associated neuronal pathways and a deficit of this hormone in the left auditory cortex.

That is what I find myself wishing. It is too close to Christmas so my thoughts turn to wishful thinking.
5 / 5 (1) Dec 22, 2011
Hypothalamic gonadotropin releasing hormone (GnRH) is the central focus of my mammalian model, and its rhythm of pulsatility regulates LH/FSH ratios steroidogenesis and neurogenesis/apoptosis. It links sensory input to all aspects of behavior associated with HPG and HPA axes regulation. The possibilities remain of much more than correlates by following the gene, cell, tissue, organ, organ system pathway that links the sensory environment directly (via gene activation) to behavior. I don't remember how to spell his last name, but Timo Jarlaveto and I have discussed the applications of this model in the processing of written language interpretable (in English) with all vowels missing from the text. Seems like language and reading may somewhat depend on socialization associated with changes in GnRH pulsate frequency. Merry Christ
not rated yet Dec 22, 2011
Thks for the seasonal wishes.
The wiki entry "Gonadotropin-releasing hormone" is an enigma for me:
Under the rubrik "Activity" is stated;
"However, once a pregnancy is established, GnRH activity is not required."
What is it about a pregnancy that is able to replace GnRH activity? Replaced with what?

All vowels missing sounds like Hebrew. Even the English language still makes sense with all vowels missing thanks to redundancy.
Seasonal tides to all.
5 / 5 (1) Dec 22, 2011
The wiki entry is also an enigma for me (as is how my Merry Christmas, turned out to be Merry Christ.) I've detailed the role of GnRH in behavioral development in a book chapter, which is available here for free:
But I have only recently begun to address the role of the placenta and prenatal/postnatal nutrition because the works I've cited are also recent works. As you can see, I tend to go overboard with the technicalities, but that's what I think is required if people are going to change the way they think about the relative salience of sensory input relevant to the timing of a properly wired brain. The variability in food preferences and sexual preferences attests to how critical the role of chemical stimuli may be to timing of GnRH pulse frequency, and thereby to everything else.
Timo's last name is spelled Järvilehto and the comparison of word identification, sans vowels, extended to the Finnish language (as I recall).
1 / 5 (1) Dec 22, 2011
Overboard?! Yes. You are far from "overboard". "Overboard" is:

"After failed attempts to infect piglets in 1984, Marshall drank a Petri dish containing cultured H. pylori,..."
later awarded (2005), ironically, with the Nobel Prize.

Science, research, and medical communities can be exasperating, frustrating experiences. To this day, the Koch postulates remain open for peptic ulcers. Fortunately, his drinking days are over proving most of what he asserted.

Once again, thanks for further reading and research - your link.
not rated yet Dec 23, 2011
As a medical laboratory scientist I'm very familiar with Marshall because we now routinely test for H.pylori. People like him are inspirational to many medical professionals. Now, if only I could cite a source that concisely explains the difference between gene activation and gene expression, I might better advise others on the requirement for a direct link to gene activation that results in gene expression. If you are familiar with a reference source that addresses this, please let me know.
1 / 5 (1) Dec 24, 2011
As orientation in your quest I turned to path analysis:

I'm sure you have access to a far more comprehensive list of mappings than the 5200 paths listed. For me, the information as orientation is helpful.

not rated yet Dec 24, 2011
Thank you, I'm not sure that providing diagrammatic representations is as effective as a narrative briefly stating that gene activation is ________: and gene expression is:_____________ in relative contexts such as sensory input and receptors and hormones and receptors.
not rated yet Dec 25, 2011
Your welcome. See you in the New Year! A wonderful commentary/post thread to end this year.

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