A readable map for all movement found deep in the brain

All possible movements an animal can do can be mapped to neural activity stored within the central brain structure known as the striatum, reveals new research that could lead to neuroscientists creating a complete atlas of movements.

The research, led by scientists from Columbia University in New York and the Champalimaud Centre for the Unknown in Lisbon, marks an important step in deciphering how the brain generates behavior and could also lead to new ways to treat disorders characterised by disrupted or repetitive movements such as Parkinson’s disease. The research is published in the journal Neuron. [ http://dx.doi.org/10.1016/j.neuron.2017.08.015 ]

“From the ears to the toes and everything in between, every move the body makes is determined by a unique pattern of brain-cell activity,” explains Rui Costa, who heads the lab investigating the neurobiology of action at the Champalimaud Centre. “Until now, using the map analogy, we only had some pieces of information, like single/isolated latitudes and longitudes, but not an actual map. This study was like looking at this map for the first time.”

The striatum has been implicated in many brain processes, most notably in learning and repeating movements. Early studies suggested cells in the striatum sent out two simple types of signals through different pathways, a kind of simple digital communication, of either ‘go’ or ‘no go’. The combination of these two signals, the theory went, drove movement.

The reality, Costa says, is more complex, with both types of neurons contributing to movement in a very specific way. “What matters is not how much activity there is in each pathway, but rather the precise patterns of activity,” he explains. “In other words, which neurons are active at any particular time, and what sorts of movements, or behaviours, corresponded to that activity.”

The researchers made their insights by observing the neural activity of genetically modified mice that had miniature mobile microscopes attached to their heads (enabling them to move relatively naturally). The microscopes captured individual activity patterns of up to 300 neurons within the striatum of each mouse brain. At the same time an accelerometer, something like a miniature Fitbit, recorded the mouse’s movements.

“We have recorded striatal neurons before,” says paper Gabriela Martins, a researcher with Columbia’s Mortimer B. Zuckerman Mind Brain Behaviour Institute. “But here we had the advantage of imaging 200-300 neurons with single-cell resolution at the same time, allowing for the study of population dynamics with great detail within a deep brain structure. Furthermore, we genetically modified the mice so that neurons were visible when they were active, allowing us to measure specific neuronal populations. This gave us unprecedented access to the dynamics of a large population of neurons in a deep brain structure.”

Working with Liam Paninski, a statistician at Columbia’s  Zuckerman Institute, the researchers devised a mathematical method to strip out background noise from their data, leaving what they describe as a clear window into the patterns of neural activity.

Says Costa: “What we saw was that for each type of movement, there is a particular pattern of brain activity, and that these patterns were organised in a specific manner.”

Similar actions were more similarly represented, while actions that were more different were represented more differently. This opens up the possibility of mapping neuronal activity to specific behaviour through detailed ensemble patterns.

“Imagine looking at the brain activity when the mouse makes a slight turn to the right versus a sharp turn,” Costa says. “In even more abstract terms, if moving my right arm is more similar to walking than to jumping, then those would be represented more similarly.

The challenge remains to find out exactly why patterns are more similar for similar actions. “Is it because it’s saying something about the body parts or muscles we’re using? This is something we hope to explore for the future”

Precisely describing the organisation of activity in the striatum under normal conditions, Costa says, is the first step toward understanding whether, and how, these dynamics are changed in disorders of movement, such as in Parkinson’s disease. “Experts tend to focus on disruptions to the amount of neural activity as playing a role in Parkinson’s but these results strongly suggest it is the pattern of activity, and specifically disruptions to that pattern, that may be more critical.”

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