A mouse creeps through a field under the cover of darkness. Suddenly, the unmistakable whiff of a fox wafts by. Instantly, blood stress hormones in the mouse skyrocket, readying the little animal to run away.
Exactly how smelling a predator triggers a hormonal response has been a mystery. Specifically, in the brain, how does the olfactory cortex communicate with the hormone-controlling hypothalamus?
US researchers claim to have found the missing link. In the journal Nature, Kunio Kondoh from the Howard Hughes Medical Institute in Maryland and colleagues traced the cells hooking up the structures, and found the part responsible for predator smell response is tiny. It comprises less than one twentieth of the olfactory cortex.
But tracing the neuronal pathway between brain regions in a mouse was not an easy job.
Mice bred in captivity were exposed to fox or bobcat urine – both natural predators – and even though they’d never smelled those odours before, they automatically generated a surge of fear hormones. But when they sniffed harmless rabbit urine, they weren’t stressed.
So to pinpoint the location in the brain from where the fear response stems, the researchers engineered a virus with a tag, which was able to jump from cell to cell. And like a tracking system, it showed which neurons were connected.
They injected the virus into a bundle of brain cells called the paraventricular nucleus, which release corticotropin-releasing hormone and eventually stimulate cortisol to be released from the adrenal gland.
The tagged virus travelled back to the olfactory cortex, but instead of infecting all the cells, the researchers saw only a small population – called the amygdalo-piriform transition area – were tagged. This part consists of only 5% of the olfactory cortex.
And when they chemically blocked the amygdalo-piriform transition area, stopping tranmission to the paraventricular nucleus, blood stress hormones also dropped. Silencing neighbouring parts of the olfactory cortex, however, didn’t have any effect.
While mice have a far more sensitive sense of smell than we do, similar hormones get activated when we are scared or stressed out. The researchers say the work will help understand how stress and fear develop in people.