http://www.eurekalert.org/pub_releases/2001-07/cuns-btf071001.php

10-Jul-2001

Cornell University News Service

Brain-development timeline for mammalian species

ITHACA, N.Y. -- A team of Cornell University neurobiologists has modeled
key milestones in brain development across nine mammalian species, from
hamsters to humans. They have, for example, pinpointed the date after
conception when the cells that make up the retina of the eye are formed.
The neurobiologists found pretty much what they expected -- an
evolutionarily conserved pattern of sequence and timing. But they also
found a few curious exceptions, such as the discovery that the human brain
is relatively developed at birth.

Knowing precisely how development in rodent brains can be translated to
other species, the researchers hope, might reduce the number of higher
animals required for research and should make transgenic mice an even more
valuable animal model in biomedical research. And because brain (neural)
development milestones are remarkably consistent in mammals, the
researchers' mathematical model is able to fill in the blanks in one
species, Homo sapiens , where experimentation is unthinkable.

One product of the model -- 95 neural development milestones for hamsters,
rats, mice, spiny mice, ferrets, cats, monkeys and humans -- is reported in
the July 2001 issue of Neuroscience (Vol. 105/1, pp. 7-17) by Barbara
Clancy, Richard B. Darlington and Barbara L. Finlay of Cornell's Department
of Psychology.

"We're happy that this model will improve estimation of the timing of
milestones in brain development, particularly for humans," says Clancy, a
postdoctoral associate in biopsychology. "This also should permit data on
the well-studied rat to be applied to the recent burst of genetic studies
in mice.

The model works because of the striking stability in the order and relative
timing of neural events across many mammalian species, including human
infants. Although their rather unwieldy bodies might disguise it, the model
shows that the brains of human infants are relatively developed at birth.

This legitimizes something that many new parents have bragged about all
along -- their baby really is quite precocious." However, Clancy says,
"we're a little disappointed that some events we humans think are important
just don't fit. We hoped we could use the mammalian model to advise when
humans should wean their young but no such luck. If humans followed the
time course set by brain development, we would wean our young immediately
after birth, and of course our kids have other ideas."

The "weaning problem" is likely related to another peculiarity in mammalian
development, Clancy notes: Relative to the sequence of neural development
events, the times required for gestation and dates of birth are "all over
the map, or rather, all over the calendar."

Some kinds of mammals are born with their eyes open, while others can't
open their eyes until hours or days after birth, she says, citing an
example familiar to anyone who has raised babies and kittens.

The only other event that doesn't fit the developmental patterns, the
Cornell neurobiologists report, is a huge surge in the production of
synapses (the junctions where brain cells communicate), an event that
begins just before birth in the developing brains of primates, including
humans.

For all other milestone events, the model accurately "predicted" the post-
conception (PC) time, where the PC time was known from actual experiments
with animals. (Accurate prediction of known facts is a critical test for
mathematical models. The model's correlation, between predictions and known
facts, was 0.9900, a nearly perfect relationship that indicates high accuracy.)

For example, the PC time of peak development of the amygdala (the
almond-shaped section in the front of the brain's temporal lobe that is
involved in emotions such as fear) was predicted by the Cornell model to be
14.3 days in rats, whereas previous experiments put amygdala development at
15 days. Similarly accurate predictions were found for amygdala development
in two other thoroughly studied species, mice and macaque monkeys.

And for species with no experimental data on that part of the brain
(including hamsters, rabbits, ferrets, cats and humans) the model made
predictions, based on the general developmental pattern in all mammals.
Thus, the PC time of peak amygdala cell development in the human fetus
should be about PC 50 days, according to the Cornell model -- although no
ethical scientist would ever conduct experiments to confirm that prediction.

"That's the beauty and power of statistical science," Darlington says.
"Because the sequence and timing pattern of neural development has been
conserved throughout the evolution of mammals, no animals were sacrificed
to compile this data.

This model could very well result in fewer animals being used in research,
and human experimentation will not be needed to increase our understanding
of events in our own neural development that we need to know about."

The new model is an outgrowth of a mathematical equation first determined
and reported in 1995 by Darlington, a behavioral statistician and professor
of psychology, and Finlay, professor and chair of the Cornell Department of
Psychology. Now the model can be used by any neuroscientist to extend
predictions of neural development milestones to any other mammalian species.

The study was supported by a grant from the National Institutes of Health
and a postdoctoral research fellowship from the National Institute of
Mental Health.

"Sorry, we just can't use this model to settle the perennial question: How
old is that dog in people years?" Finlay says. "But if you give us a
minute, we can tell you exactly when a fetal dog's amygdala appears."

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Related World Wide Web sites: The following sites provide additional
information on this news release. Some might not be part of the Cornell
University community, and Cornell has no control over their content or
availability.

o Neuoscience journal: http://www.elsevier.com/locate/neuroscience

o Cornell Dept. of Psychology: http://comp9.psych.cornell.edu/