Oxytocin alters mind exercise to spice up sociability in mice lacking autism gene | Spectrum
Social Boost: In a mouse model with impaired social behavior, an oxytocin injection activates a specific set of circuits.
publisher’s Note
This article was originally published as Conference Proceedings from the 2021 Society for Neuroscience Global Connectome Meeting on January 13, 2021. The results have since been published in Neuron.
Infusions of the hormone oxytocin make mice that model autism more social by normalizing patterns of brain activity. The researchers presented the results virtually at the 2021 Society for Neuroscience Global Connectome yesterday. (Links to abstracts may only work for registered conference attendees.)
The mice lack a gene called CNTNAP2, which when mutated in humans is linked to autism, language disorders and altered brain connectivity. The animals also have unusually few oxytocin-producing neurons and show little interest in mixing with other mice.
“[They] don’t spend a lot of time interacting with a new partner, and when you give oxytocin, the interaction time more than doubles,” says lead researcher Katrina Choe, assistant professor of psychology, neuroscience, and behavior at McMaster University in Hamilton, Ontario . Canada.
In the new work, Choe and her colleagues took snapshots of brain activity in mice after they injected them with oxytocin. The injection did not affect brain activity in control mice, the researchers found. But in mice lacking CNTNAP2, it activates several brain regions to which oxytocin-producing neurons are normally attached, including a reward-associated region called the nucleus accumbens.
The researchers then imaged the mice’s brains at rest to compare the level of connectivity within brain regions related to social behavior and between social regions and other brain areas.
In CNTNAP2 mice, connections between social brain areas are weaker than in control mice, but connections between social regions are unusually strong. But an oxytocin injection normalizes this pattern, increasing bonding between social brain areas and reducing it elsewhere. In particular, oxytocin strengthens the connections between three different pairs of brain regions, one affecting the medial prefrontal cortex and another affecting the nucleus accumbens.
“We identified several interesting circuits and connections that may underlie the effects of oxytocin on social behavior,” says Choe.
Flowing from within:
To see how oxytocin affects brain activity when produced internally rather than injected, the researchers selectively stimulated oxytocin-secreting neurons in the hypothalamus. The team found that it was these switched-on oxytocin neurons that activated the nucleus accumbens the most.
Finally, the researchers used a technique called optogenetics to selectively turn oxytocin secretion on and off only in the nucleus accumbens. When oxytocin flows into the region, CNTNAP2 mice enthusiastically interact with another mouse, the team found, but when that flow is stopped, the mice return to their solitary ways. No manipulation affects control mice.
“We have accumulated a lot of converging evidence suggesting that the nucleus accumbens may be a key region” to modulate social behavior via oxytocin, says Choe.
Read more reports from the 2021 Society for Neuroscience Global Connectome.
