DEPRESSION
November 30, 2012

Tracing Motivation's Path

An ingenious way of lighting up brain networks shows researchers what prompts us to act and offers a clue to depression.

Motivation — the ability to decide whether an activity is worth the energy it will cost — is a process fundamental to most organisms. We humans use it countless times per day, deciding whether to make that second cup of coffee or whether to go for that second Masters degree or lap around the park. It’s a complex process, and until now, researchers have not understood much about how it works in the brain.

The brain’s prefrontal cortex is the place where motivation has been believed to take place, along with a handful of other high-level processes, like decision-making, social behavior, and abstract thinking. A new study not only confirms this belief, but actually illustrates the networks of brain cells that are involved, from the “highest” point – the prefrontal cortex – down to the cells of the motor cortex which help carry out the physical action to go along with motivation.

The raphe nucleus is important because it produces serotonin, the brain chemical that is targeted in antidepressant medications. A lack of motivation, which can range from mild to almost crippling, is one of the defining features of depression.

In order to see which networks of cells are activated when an animal carries out an activity, the research team used light-sensitive proteins made by green algae. The gene for the protein, channelrhodopsin, can be engineered and placed into the brain cells of rodents so that light can be applied to the cells to activate them.

Simply activating cells in the prefrontal cortex didn’t make the animals any more likely to perform an action. “It’s one step more subtle,” said lead author Karl Deisseroth in a news release. So the researchers used another method — projection targeting. First they placed the light-sensitive protein into the prefrontal cortex, and watched as it worked backward, following the nerve pathways it spread along, like branches, all the way down to the brain stem. Having found the end of the chain, they applied light to the brain stem, and looked at which subgroups of brain cells in the prefrontal cortex were activated.

When a specific pathway was stimulated (between the prefrontal cortex and an area of the brain stem called the dorsal raphe nucleus) animals showed a distinct burst in motivation.

The raphe nucleus is important because it produces serotonin, the brain chemical that is targeted in antidepressant medications. A lack of motivation, which can range from mild to almost crippling, is one of the defining features of depression. Along these lines, the researchers were also interested to find that when they stimulated another brain area thought to play a role in depression, the lateral habenula, the animals were less likely to carry out actions.

Understanding how motivation works in both the healthy brain and in those with mental illnesses will help researchers develop better treatments for brain disorders and diseases. According to Deisseroth, just helping a person with a mental illness understand that his or her symptoms are due to blips in brain circuitry can be a great relief, and a motivating factor in and of itself.

The research was carried out at Stanford University and published in the journal, Nature.

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