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Motherhood May Permanently “Rewire” the Mouse Brain

A white laboratory mouse.
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Pregnancy hormones can promote parental behavior in mice by altering a small region of neurons in the brain, suggests a new study. The research, which suggests that this “rewiring” leads to stronger parental responses to pups, is published in Science.

Hormonal changes and maternal behavior

It was previously thought that maternal behavior is likely to be brought about by the release of hormones when giving birth. This is because female virgin mice show little interest in or interaction with mouse pups, yet the majority of a mouse’s time after motherhood is taken up by looking after their offspring.

However, evidence of maternal behavior has been found in rats that delivered offspring via cesarean section or indeed virgin mice exposed to pregnancy hormones. This suggests that mechanisms driving maternal behavior may start during pregnancy – earlier than previously thought.

Until now, it was not well understood exactly how pregnancy hormones can remodel the brain to prepare for parenthood. In the current study, researchers from the Francis Crick Institute investigated these neural changes in more detail, finding that female mice did indeed show increased parental behavior during late pregnancy and that this change did not require exposure to pups.

Remodeling of parental brain circuits

The researchers, led by Dr. Jonny Kohl, group leader in the State-Dependent Neural Processing Laboratory at the Francis Crick Institute, focused their investigation on a population of nerve cells called galanin-expressing neurons.

These are found in the hypothalamus within an area associated with parenting called the medial preoptic area (MPOA). In their experiments, Kohl and colleagues found that estrogen and progesterone were able to impact these galanin-expressing neurons.

Brain recordings showed that estrogen both reduced their baseline activity and made them more excitable, while progesterone rewired their inputs by recruiting more synapses (used by neurons to communicate with each other).

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They also found evidence that there is a critical period during pregnancy when these hormones can take effect. By experimentally rendering the neurons insensitive to these hormones, they were able to completely remove signs of parental behavior both during pregnancy and after giving birth. Some of these changes lasted for at least a month after birth, while others seemed to be permanent, suggesting the brain can be rewired in this way long-term.

"We know that the female body changes during pregnancy to prepare for bringing up young. One example is the production of milk, which starts long before giving birth. Our research shows that such preparations are taking place in the brain, too,” Kohl explained. “We think that these changes, often referred to as ‘baby brain’, cause a change in priority – virgin mice focus on mating, so don’t need to respond to other females’ pups, whereas mothers need to perform robust parental behavior to ensure pup survival. What’s fascinating is that this switch doesn’t happen at birth – the brain is preparing much earlier for this big life change.”

Evidence for “baby brain”?

“We’ve demonstrated that there’s a window of plasticity in the brain to prepare for future behavioral challenges,” explained Dr. Rachida Ammari, co-lead author of the study and postdoctoral fellow at the Francis Crick Institute. “These neurons receive a large number of inputs from elsewhere in the brain, so now we’re hoping to understand where this new information comes from.”

Importantly, the researchers emphasize that the pups’ welfare was always maintained during the study, with foster mothers introduced to care for the pups where appropriate. They believe that the human brain could also be rewired in a similar way during pregnancy, with the same areas of the brain predicted to be influenced by these hormonal changes, potentially influencing parental behavior.

Reference: Ammari R, Monaca F, Cao M, et al. Hormone-mediated neural remodeling orchestrates parenting onset during pregnancy. Science. 2023;382(6666):76-81. doi: 10.1126/science.adi0576

This article is a rework of a press release issued by the Francis Crick Institute. Material has been edited for length and content.