Hormones and the neurobiology of being in the mood (illustration: Gil Costa)

In the first part of this 3-part series, Susana Lima, head of the Neuroethology lab at Champalimaud Centre for the Unknown, told us about her work on mate choice, a process by which individuals find “the one”.  But as we all know, just because we think we found “the one” today, it doesn’t necessarily mean that we’ll be in the mood to see them again tomorrow, not to mention for the rest of our lives… Why is that? What internal changes make us respond differently to the same person?

“With humans it’s quite complicated and there are many factors that play a part, but in mice it’s more straightforward. The answer is hormones. Similarly to humans, the reproductive cycle of mice, called the estrous cycle, is regulated by the shifting levels of the hormones estrogen and progesterone. It was already known that these hormones are strong modulators of behaviour in mice, implying that they work not only on the level of the reproductive organs, but also on the brain. What is not yet fully known is precisely how these hormones influence the activity of neural circuits in the brain.”

Susana became interested in this topic in what one might call an unusual way: “While working on mate choice I ended up spending a lot of time watching videos of ‘mouse porn’”, she laughs, “and became fascinated by the range of behaviours I was observing, specifically those displayed by females during different phases of their reproductive cycle. Depending on the female’s internal state, namely her ability to become pregnant, responses to brief social interactions with males could result in radically different outcomes, ranging from receptivity to downright aggression.”

Together with Kensaku Nomoto, a postdoctoral researcher in the lab at the time, Susana chose to investigate the neural circuits that underlie these polar behaviours by focusing on an area in the brain called the hypothalamus. “We know that the hypothalamus regulates many instinctive behaviours, including feeding, sleep and sexual behaviour and so, we decided to record the activity of neurons in an area that is dedicated to socio-sexual behaviour while females were interacting either with males or with other females.” she explains.

“We found that the activity of these neurons changed depending on the reproductive state of the female. When pregnancy was not possible, the activity of the neurons was similar during social encounters with either males or females. However, when pregnancy was possible, the activity of the neurons was enhanced only when interacting with males.”  These results, published in February 2015, represent the first time that the activity of these neurons was recorded in naturally cycling females. “It established that there is in fact a brain region where information about hormonal state and social interaction are integrated”, says Susana.

Why would the brain need to integrate these two different types of information? “Imagine that you are an animal in the wild. To be safe, your brain needs to balance out two processes that are happening simultaneously: attraction and defence. So even though you would normally lean towards a ‘fight or flight’ response when coming across a stranger that could be potentially dangerous, your hormonal state gets you ‘in the mood’ while lowering your baseline defences. Actually, some of the neurons we recorded from communicate with the brain region that generates the ´fight or flight’ response, suggesting that these neurons may have a direct route to impact the behaviour of the animal.”

This finding sparked a series of parallel studies in the lab aimed at elucidating the neural circuitry that underlies the influence of hormones on the brain. The team uses techniques that target individual neurons in the brain by combining genetic and optical tools.

“For me, one of the most remarkable aspects of sex is that it competes with our strong natural defencive behaviours. To understand how this happens, we are now crossing information about the activity of populations of neurons in the brain with anatomical mapping of the connections across different regions. This is where we are at this moment and it’s very exciting.” Susana concludes.     

Part 1: Finding “the one”.

Part 3: A happy ending is only the beginning. 




Liad Hollender works as a Science Writer at the Science Communication Office at Champalimaud Research



Edited by: Catarina Ramos (Science Communication office)
Illustration Credit: Gil Costa



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