A region in the brainstem, called the median raphe nucleus, contains neurons that control perseverance and exploration.Credit: K H Fung/Science Photo Library
Whether mice persist with a task, explore new options or give up comes down to the activity of three types of neuron in the brain.
In experiments, researchers at University College London (UCL) were able to control the three behaviours by switching the neurons on and off in a part of the animals’ brainstem called the median raphe nucleus. The findings are reported in Nature today1.
“It’s quite remarkable that manipulation of specific neural subtypes in the median raphe nucleus mediates certain strategic behaviours,” says neuroscientist Roger Marek at the Queensland Brain Institute in Brisbane, Australia, who was not involved in the work.
Whether these behaviours are controlled in the same way in humans needs to be confirmed, but if they are, this could be relevant to certain neuropsychiatric conditions that are associated with imbalances in the three behavioural strategies, says Sonja Hofer, a co-author of the paper and a systems neuroscientist at UCL.
For instance, an overly high drive to persist with familiar actions and repetitive behaviours can be observed in people with obsessive–compulsive disorder and autism, she says. Conversely, pathological disengagement and lack of motivation are symptoms of major depressive disorder, and an excessive drive to explore and inability to persevere with a task is seen in attention deficit hyperactivity disorder. “It could be that changes in the firing rate of specific median raphe cell types could contribute to certain aspects of these conditions,” says Hofer.
Light ‘switch’
The researchers genetically engineered the three types of neuron — which release the neurotransmitters GABA, glutamate and serotonin — in the median raphe nucleus of mice to express a light-responsive protein, which meant the neurons could be switched on and off using light. Mice were then placed in a box with 20 objects they had never seen before.
A group of control mice spent roughly equal amounts of time pursuing each of the three strategies: persisting in their interaction with one object by grabbing, carrying or biting it; exploring their options by interacting with many objects over a short period of time; or ignoring the objects and disengaging.
When the researchers suppressed GABA-releasing, or GABAergic, neurons, mice persisted with individual objects for longer and switched between objects less frequently than control mice did. By comparison, activating the glutamatergic neurons — even for just two seconds — caused mice to spend more time leaping from one object to another in quick succession, indicating increased exploration.
Even brief suppression of serotonergic neurons triggered the mice to spend more time in a disengaged state. The study also found that a midbrain region called the lateral habenula was involved in suppressing serotonergic neurons in the median raphe nucleus, causing the mice to disengage from tasks.
“This is a really elegant and intriguing study,” says behavioural neuroscientist Mark Walton at the University of Oxford, UK.
