Fearless mice are neglectful mothers but social butterflies

We like to idolise fearlessness and we equate it to bravery but there is a fine line between that and stupidity. Immunity to the pangs of fear would leave someone unable to assess threats to themselves and to other people, which means that fear not only has consequences for an individual but for their entire social circle. Guillaume Martel and colleagues from Rutgers University demonstrated these far-reaching consequences by examining a special group of mice which had been genetically engineered to be fearless.

Martel's team focused their attention on the amygdalae, a pair of almond-shaped structures, one in each half of the brain, that play an important role in emotion, and particularly in creating and storing memories linked to emotional events. Each amygdala can be divided up into a few distinct regions depending on their role and which other parts of the brain they connect to. One of these regions - the basolateral complex, or BLA- is specifically involved in learning about fear.

The team worked with mice that were missing a gene called stathmin, which is particularly active in the basolateral amygdala. In previous research, they had already showed that removing this gene switches interferes with a mouse's ability to fear. Not only are they inherently bolder than their normal littermates, they also fail to record long-term memories about frightening experiences.

This time, Martel showed that the loss of stathmin also turns female mice into neglectful ones. In a normal situation, a virgin female would react strongly to the sight of abandoned pups, even foster ones. If three isolated pups are placed in the far corner of a female's cage, she would quickly bring them over to her nest within about three minutes. But not if her basolateral amygdalae isn't working properly -the stathminÂ-less mice took much longer (about 10 minutes or so) to retrieve the pups.

In other respects, the neglectful mice behaved normally - they clearly recognised the pups when they eventually approached them, they built regular nests, they were active, and their senses of smell were working well. But they were sorely lacking when it came to infant care and Martel thinks that this was because they are unable to properly assess the threats that the pups face.

Danger Will Robinson!

This defect became very clear when the researchers broke their nests up, scattered the pieces around their cages and placed three random pups among them. Faced with the task of rebuilding, normal mice gathered the pieces in the safest places, choosing a corner about 75% of the time and along a wall about 20% of the time. But the stathmin-less mice didn't care about the extra safety provided by the walls and were just as likely to build their nests in the middle of the arena - the most dangerous and exposed place for the pups.

This disregard took its toll on the pups. When the altered females were allowed to raise their own litters, their pups weighed far less than those raised by normal mothers during their first week of life, when they are particularly dependent on care. In the longer term, their chances of survival were lower too.

These differences had everything to do with fear (or lack of it) and nothing to do with other aspects of motherly behaviour. Stathmin is concentrated in the circuits of the basolateral amygdala and it isn't active in other parts of the brain that drive maternal care. Indeed, neuronal activity in these other areas was par for the course in the altered mice. Various hormones, such as oxytocin, also affect motherly behaviour but again, a lack of stathmin didn't alter the levels of these chemicals.  

In contrast to their attitudes to pups, Martel also found that with stathmin removed, the rats were more sociable with other adults. When given the option, they spent about twice as long socialising with other female rats as normal individuals did, and they reacted curiously and not aggressively to strangers who were placed in their cages. Martel suggests that it is the same tendency to downplay threats that leads mice to be more open with their contemporaries, while more reckless with their own (and their pups') wellbeing.

Martel also ran all the same tests with normal mice whose genes were all intact but whose basolateral amygdalae had been deliberately damaged. They reacted to pups, open spaces and other mice in the same way as those whose stathmin gene had been removed. It's further proof that the neural circuits of the basolateral amygdale, in affecting the learning of fear, are also involved in social interactions and motherly behaviour. Martel even suggests that targeting the stathmin gene may have some use in helping people with disorders that make them overestimate threats or hamper their social lives - anxiety disorders and autism, to name a few.

Reference: PNAS doi: 10.1073/pnas.0807507105