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Developmental biology - Brain

Clues On Why Brain Does or Doesn't Mature

Physical myelination of axons in adolescence may lead to higher or lower intellectual ability...


One of the outstanding questions in neurodevelopment is what changes during childhood and adolescence to improve brain function. Now, a study in rats conducted at the University of Massachusetts Amherst (UMass) may give us an answer. Neuroscientists Heather Richardson, Geng-Lin Li and colleagues suggest that changes to axons during adolescence speed up neural transmissions - and may or may not lead to higher intellecual ability.
"One advantage of increased conduction speed is faster processing of information; brain areas communicate faster and decisions can be made faster. A thin axon will be slower, a thick one faster. Myelin [the coating around axons] can also make axons faster."

Andrea Silva-Gotay, Neuroscience and Behavior Graduate Program, University of Massachusetts, Amherst, Massachusetts, USA and co-author.

Richardson and colleagues study axons. These are the long nerve threads along which signals are conducted from one nerve cell to another. The are wrapped in myelin - an electrically insulating sheath which forms during juvenile and pre-adolescent rat stages - or 15 days old to mid-adolescence at 43 days old.

Neuron
Image: David Baillot University of California San Diego

Writing in the journal eNeuro, Richardson says they have identified specific changes in developmental thought to be key to the medial prefrontal cortex (mPFC) of a maturing rat brain. The mPFC region integrates information from many sources. It processes and modifies complex responses to stress - while controlling behavior, attention and memory. Research results suggest in two-to-six week old rats, mPFC axons undergo microstructural and electrophysical change that speeds up neural transmissions.
Silva-Gotay explains: "Between those two ages we found a significant increase in how fast electrical signals travel in the brain during pre-adolescence - compared to adolescence. There is a dramatic increase. Moreover, we found this in the mPFC - which was not known before."

Andrea Silva-Gotay, Neuroscience and Behavior Graduate Program, University of Massachusetts, Amherst, Massachusetts, USA.

The authors saw that signal conduction velocity in axons nearly doubled by mid-adolescence, which corresponded with a 90-fold increase in the number of myelinated axons in that region.
"Because axonal diameter did not change with age, we reason that myelination of axons accounts for their significant increase in speed. These axonal changes may be contributing to developmental improvements in how the prefrontal cortex works."

Heather N. Richardson PhD, Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, Massachusetts, USA, and senior author.

Richardson and Silva-Gotay suggest this represents myelination patterns in other animal brains around this same time of development. Electrical signals could be traveling along axons at a faster pace in these same regions as well.
Prefrontal Cortex of Rat in hatched lines

Prefrontal Cortex of Human in hatched lines

Pre Frontal Lobe of rat and human indicated with hatched lines.
Image source: Frontiers in Neural Circuits.

"It is also important to consider factors that could interfere with this myelination process. We and others have found alcohol can reduce myelin in this part of the brain. It is possible transmission speed in these axons is negatively affected as well.

Heather Richardson PhD

Abstract
Myelination of prefrontal circuits during adolescence is thought to lead to enhanced cognitive processing and improved behavioral control. However, while standard neuroimaging techniques commonly used in human and animal studies can measure large white matter bundles and residual conduction speed, they cannot directly measure myelination of individual axons or how fast electrical signals travel along these axons. Here we focused on a specific population of prefrontal axons to directly measure conduction velocity and myelin microstructure in developing male rats. An in vitro electrophysiological approach enabled us to isolate monosynaptic projections from the anterior branches of the corpus callosum (corpus callosum-forceps minor, CCFM) to the anterior cingulate subregion of the medial prefrontal cortex (Cg1) and to measure the speed and direction of action potentials propagating along these axons. We found that a large number of axons projecting from the CCFM to neurons in layer V of Cg1 are ensheathed with myelin between pre-adolescence (postnatal day 15) and mid-adolescence (postnatal day 43). This robust increase in axonal myelination is accompanied by a doubling of transmission speed. As there was no age difference in the diameter of these axons, myelin is likely the driving force behind faster transmission of electrical signals in older animals. These developmental changes in axonal microstructure and physiology may extend to other axonal populations as well, and could underlie some of the improvements in cognitive processing between childhood and adolescence.

Significance
Neural processing improves during childhood and adolescent development, but the specific factors contributing to these developmental changes are largely unknown. The present study shows that between two and six weeks of age in male rats, axons in the prefrontal cortex undergo microstructural and electrophysiological changes that speed up neural transmission. These axonal changes could contribute to some of the developmental improvements in behavioral control and cognitive abilities dependent on the prefrontal cortex.

Authors
Sean McDougall, Wanette Vargas Riad, Andrea Silva-Gotay, Elizabeth R. Tavares, Divya Harpalani, Geng-Lin Li and Heather N. Richardson.

Authors report no conflict of interest.


Funding sources
This work was supported by NIH/NIAAA awards R01AA024774 and R21AA021013 to HNR; NIH/NIDCD awards R00DC010198 and R01DC015475 to GLL; NIH/PREP award R25GM086264 to WVR The work was also funded by grants from NIH's National Institute on Alcohol Abuse and Alcoholism to Richardson, a National Institute on Deafness and Other Communication Disorders grant to Li and an NIH Post-baccalaureate Research Education Program grant to Vargas Riad.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.


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Oct 1, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




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