'Mini' microscopes shed light on social behaviour


Rebecca Pool

Thursday, November 2, 2017 - 15:00
Image: When mice meet, different brain activity patterns light up; in the medial amygdala, some neurons respond to males (green), some respond to females (red), and other neurons respond to both sexes (yellow), [Catherine Dulac Lab]. 
Miniature microscopes mounted on mice's heads have provided insight to the neural circuitry of social behaviour in these animals.
Instincts such as mating or fighting are innate behaviors generally thought to be hardwired into an animal's brain.
But now, two studies that map brain activity in living mice reveal that social experiences can influence brain responses to other mice.
The results, recently reported in Nature and Cell, show how and where in the brain some instincts are shaped by learning, says Howard Hughes Medical Institute Investigator David Anderson of California Institute of Technology.
"We're starting to get a sense of what happens between the part of the brain that takes in sensory information and the part that produces behaviour," he says.
Working independently, Anderson and fellow HHMI Investigator Catherine Dulac of Harvard University mapped patterns of brain activity in different brain regions while mice sniffed, ignored, fought, or mated with other mice.
Dulac and her team tracked brain activity in the medial amygdala, an almond-shaped structure that transmits smell signals to the hypothalamus.
First, the researchers introduced a protein to the mice, to light up active brain cells.
They then mounted lightweight miniature microscopes, manufactured by nVista for one-photon epifluorescence imaging of calcium dynamics, onto the heads of individual mice.
They then studied which brain cells were active when each camera-wearing mouse met another mouse.
A thin glass rod implanted in the amygdala collected light from active brain cells and served as the microscope's lens.
The researchers recorded neural activity while videotaping the mice's behavior in different social situations.
Dulac's team observed that different clusters of neurons lit up when mice met a member of the opposite sex.
These sex-specific neural patterns were quite different while the act of mating also transformed the brain's activity patterns. 
And, after housing 'virgin' mice in a cage with a mouse of the opposite sex for 15 days, the mice had long-lasting changes in the brain.
"It was surprising to see patterns of brain activity thought to be instinctively activated by odour actually change with experience - and stay changed for over a month," highlights Dulac.
Meanwhile, at Caltech, Anderson and colleagues also wanted to visualise the neural circuitry involved with social behaviour in male mice.
The researchers used the same microscopic technique as Dulac's team but implanted the lens in the ventromedial hypothalamus, an evolutionarily ancient structure involved in social behaviour.
Anderson's team then imaged the activity of a specific population of neurons that produce the estrogen receptor, which is well known for its influence on social behaviors.
The team placed the microscopes on virgin, socially isolated male mice and let them interact in an alternating manner with five different females and five different males, each for two minutes, for several consecutive days.
The researchers imaged the same neurons across multiple trials and multiple days, and correlated changes in neural activity with changes in social behaviours, such as sniffing, mounting, and attacking.
"We watched activity patterns change in real time as a mouse's brain learned to tell the difference between males and females," says Anderson.
According to the researcher, the latest research suggests that although mating and fighting are innate behaviours, mice's brains have to learn to tell the difference between males and females before they can properly exhibit both of these behaviours.
His team's findings also reveal that neural activity in the hypothalamus is dynamic, and can be shaped by experience.
Anderson reckons these properties indicate that this evolutionarily ancient region of the brain may be more similar to newer brain regions than previously thought.
Altogether, the current work has given researchers a detailed look into the neural circuitry underlying mouse social behaviour.
As Dulac says: "It's wonderful to have a flurry of information about what the brain of an animal says as it meets another animal and how that changes with different social experiences. For me, this is a bit of a dream come true."
Research is published in Nature and Cell.
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