Center for Behavioral Neuroscience (CBN) researchers
have demonstrated that genetically identical mice placed in different
environments both pre- and post-natally differ dramatically as adults
in their stress responses and learning abilities. The finding, reported
in the May issue of Nature Neuroscience, suggests that
pre- and post-natal maternal environments, when taken together,
play a strong role in determining the stress profile and cognitive
development of genetically identical mice.
In the study led by Darlene Francis, a postdoctoral fellow at Yerkes
National Primate Research Center, and Thomas Insel, former CBN director
and current director of the National Institute of Mental Health,
the scientists selected two inbred mouse strains known to differ
in their stress reactivity (high versus low) and cognitive performance.
All the mice within each strain were identical.
To gauge the influence of different uterine and early-life environments
on development, the scientists transferred embryos from recently
mated low-stress (B6) female mice to female surrogates from the
strain that displayed high-stress reactive profiles (BALBs). For
comparison, they also transferred embryos to surrogate females within
the same strain.
At birth, all mice were cross-fostered again and reared by either
a low-stress B6 mother or a high-stress BALB mother. At three months
of age, when all of the offspring reached adulthood, the researchers
compared their stress reactions and cognitive performance.
The low-stress B6 mice transferred as embryos to and also later
reared by surrogate BALB females demonstrated an increase in stress-reactive
behaviors. These mice were less likely to explore new environments
than their genetically identical counterparts that were carried
and reared by low-stress mothers. The low-stress B6 mice reared
by surrogate BALB females also performed more poorly on cognitive
tests of their ability to navigate mazes.
“We completely reshaped the presumed genetic differences by
changing the pre- and post-natal environmental conditions,”
Francis said. “The maternal care received by the mice, in
addition to the uterine environment, produced a cascading effect
on the animals’ stress profile and cognitive performance.”
Despite the growing conviction that genetics determine development,
Francis said the findings of her study demonstrate the significant
role of the environment in regulating certain behaviors.
Francis and her colleagues currently are examining brain receptors
in the inbred mice that were transferred to and later reared by
surrogate females to determine changes that may have occurred as
a result of their pre- and post-natal environmental conditions.
In their next experiment, the CBN team will examine whether mice
bred from high-stress mice can develop into low-stress animals when,
during development, they are exposed to low-stress maternal environments.
“There clearly were some behaviors—such as pre-pulse
inhibition, a measure of the ability to integrate sensory information—that
our early environmental manipulations could not regulate,”
Francis said. “However, our current observations support previous
research that the prenatal environment interacts with the postnatal
environment to shape stress-associated behaviors and cognitive performance
In addition to Francis and Insel, other study co-authors included
Emory/Yerkes researchers Kathleen Szegda, Gregory Campbell and David