Early-life environments shape development of stress behaviors and learning abilities in mice

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, PhD, a postdoctoral fellow at Emory University’s Yerkes National Primate Research Center, and Thomas Insel, MD, former director of the CBN and current director of the National Institute of Mental Health, the scientists selected two in-bred mouse strains known to differ in their stress reactivity (high versus low) and cognitive performance. All the mice within each in-bred 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 purposes, 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. When all of the offspring reached adulthood at three months of age, the researchers compared their stress reactions and cognitive performance. The low-stress B6 mice that were 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 between the in-bred mouse strains by changing the pre- and post-natal environmental conditions,” said Francis. “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 are currently examining brain receptors in the in-bred 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 were clearly some behaviors such as prepulse inhibition, a measure of the ability to integrate sensory information, that our early environmental manipulations could not regulate,” said Francis. “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 adulthood.”

In addition to Francis and Insel, co-authors of the study are Emory University/Yerkes researchers Kathleen Szegda, Gregory Campbell, and Emory pathologist W. David Martin, PhD

The Center for Behavioral Neuroscience, a Science and Technology Center funded by the National Science Foundation, is a research and education consortium consisting of eight universities in the Atlanta area. CBN researchers study four aspects of behavioral neuroscience: fear, aggression, affiliation, and reproduction.