For example, they have observed that stress incurred early in life attenuates neural growth. Now a new study with male mice exposed to stress shows that the hippocampus reaches some developmental milestones early—essentially maturing faster in response to stress.
The findings, the first to track and report signs of stress-related early maturation in a brain region as mice develop, may lend some credence to the expression that children facing early adversity have to “grow up too fast.”
Kevin Bath, assistant professor of cognitive, linguistic, and psychological sciences at Brown University, became curious about whether some brain regions were maturing faster when he observed that certain traits in humans and rodents—such as fear-driven learning and memory, sexual development, and neural connectivity among some brain regions—were accelerated, rather than stunted, after early life stress. Some of these qualities, particularly memory and emotion regulation, involve the hippocampus.
“There were a number of different indicators that [early maturation] might be happening,” he says. “We wanted to carefully assess this and look at a number of different markers of not only growth, but also maturation of these animals, and to measure it not only at the behavioral level but also at the neuromolecular level.”
For the study, published in the journal Hormones and Behavior, researchers exposed the mice to a period of fragmented maternal care—a condition comparable to one that might affect a child growing up in an economically challenged, single-parent household, for example.
At four days of age, pups and their mothers were moved from standard cages to ones where the materials available to the mother for nest building were inadequate. Food and water remained plentiful, but the mother responded anxiously and would frequently depart to search for anything that might work as nesting material.
Pups therefore received less consistent and attentive care from their harried and distracted mothers than experimental controls that were never moved from standard cages. After just a week of exposure to this manipulation (a significant span of time for mice who mature from birth to adulthood in just eight weeks), the mice returned to cages with everything they needed.
By then, however, the effects of the stress were already well underway. Researchers made several measurements in mice at 4 days and at 50 days (when mice reach young adulthood) to track how development in the hippocampus varied between mice exposed to stress and the unstressed controls.
Focus on short-term priorities
What they found—from counting specific populations of cells, measuring behavior, and gene expression—was that the hippocampus appeared to mature significantly faster in the stressed mice during their seven weeks from birth to early adulthood.
Based upon measures of gene expression and counting cells, the team saw that parvalbumin interneurons developed about a week early, attaining an abundance by day 21 in stressed mice that was not seen in control mice until day 28. In other measurements, the teams saw that developmental changes in synaptic receptor subunits that are important for developmental changes in learning occurred about nine days ahead of schedule. They also found that myelination, a key developmental process for neural communication, also started more than a week early.
They also looked at a behavioral trait controlled by the hippocampus. Mice can be conditioned to associate shocks with a particular location, such that they will freeze in fear when they come back to that place. But for about a week during the maturation of the hippocampus, that freezing behavior temporarily disappears. In the new study, this was still the case, but the temporary suspension of the fear response happened a week earlier in stressed mice than in control mice.
The results showing reduced growth but faster hippocampus maturation appear to support an evolution-based hypothesis that mice—and perhaps people, too—interpret early stress as a cue to adapt brain development to match a world where long-term survival seems unlikely, Bath says.
“In the case of development, the stress may be providing a signal about the hospitability of the environment.”
In other words, rather than invest for the long run in optimally refined systems in the cortex for learning rules and suppressing emotional responses, mice may instead invest in accelerating the maturation of more primal systems, such as the hippocampus, to support short-term priorities, like racing to survive long enough to reproduce at least once.
“The evolutionary push is for you to pass on your genes,” Bath says. “We hypothesize that stress drives a reallocation of developmental resources from development of the full brain to development of limbic structures that are important for reproduction.”
The Brown Institute for Brain Science, Robert and Nancy Carney, and the Brain & Behavior Research Foundation funded the research.