Imagine you are playing the guitar. You’re seated, supporting the instrument’s weight across your lap. One hand strums; the other presses strings against the guitar’s neck to play chords. Your vision tracks sheet music on a page, and your hearing lets you listen to the sound. In addition, two other senses make playing this instrument possible. One of them, touch, tells you about your interactions with the guitar. Another, proprioception, tells you about your arms’ and hands’ positions and movements as you play. Together, these two capacities combine into what scientists call somatosensation, or body perception.
Our skin and muscles have millions of sensors that contribute to somatosensation. Yet our brain does not become overwhelmed by the barrage of these inputs—or from any of our other senses, for that matter. You’re not distracted by the pinch of your shoes or the tug of the guitar strap as you play; you focus only on the sensory inputs that matter. The brain expertly enhances some signals and filters out others so that we can ignore distractions and focus on the most important details.
How does the brain accomplish these feats of focus? In recent research at Northwestern University, the University of Chicago and the Salk Institute for Biological Studies in La Jolla, Calif., we have illuminated a new answer to this question. Through several studies, we have discovered that a small, largely ignored structure at the very bottom of the brain stem plays a critical role in the brain’s selection of sensory signals. The area is called the cuneate nucleus, or CN. Our research on the CN not only changes the scientific understanding of sensory processing, but it might also lay the groundwork for medical interventions to restore sensation in patients with injury or disease.
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To understand what’s new, we should review a few basics of how somatosensation works. Whenever we move or touch something, specialized cells within our skin and muscles respond. Their electrochemical signals travel along nerve fibers to the spinal cord and brain. The brain uses these messages to track body posture and movement and the location, timing and force with which we interact with objects. Experiments have made clear that the conscious experience of our body and its interactions with objects relies on these signals reaching the cerebral cortex, the outermost layer of the brain. Scientists have long assumed that this brain area was one of the main players involved in selectively enhancing or filtering sensory signals. They believed that the CN, on the other hand, was simply a passive relay station, moving signals from the body up to the cortex.
But we were skeptical. Why would the CN exist if it does not alter the signals in some way? We decided to watch cuneate neurons in action to find out. The challenge historically has been that the CN is small and very hard to access. It’s located at the highly flexible junction of head and neck, meaning an animal’s movement can make it difficult to reach. To make matters worse, the cuneate nucleus is nestled in the brain stem, surrounded by vital brain regions that, if damaged, can lead to death.
Fortunately, modern neuroscientific tools let us observe the CN stably in awake animals without harming nearby areas. In monkeys, we implanted tiny arrays of electrodes that we used to monitor individual cuneate nucleus neurons. For the first time, we could study how single brain cells in this area respond when a monkey moved and touched things. This method allowed us to answer several questions about what the CN does. For one, we studied how these neurons respond to touch signals by exposing monkeys’ skin to many kinds of stimuli, including vibrations and braille-like embossed dot patterns. We then compared the responses in the CN with activity in nerve fibers that feed into this brain structure. If the area just passed along information collected by the skin’s sensory cells, neural activity in the CN would essentially echo the activity in nerve fibers. Instead, we found that CN neurons do not simply pass their inputs along but transform them. In fact, cuneate neurons showed patterns of activity that were more similar to those in the brain’s cerebral cortex neurons than they were to the patterns in nerve fibers.
But the connection between CN and cortex is not a one-way street. In addition to sensory nerves going up, there are pathways from sensory and motor areas of the cerebral cortex going down to the cuneate nucleus. We wondered whether the CN contributes to some form of sensory filtering based on an animal’s planned voluntary movements. To that end, we observed CN activity when monkeys reached toward a target and compared those signals with the CN signals generated when a robot moved the monkeys’ arm in a similar fashion. We discovered that the activity in cuneate neurons did indeed change, depending on what the animals were doing and whether movements were voluntary or involuntary. As just one example, we know that signals from arm muscles can help an animal determine that a movement is going as planned. In line with this idea, we found that many signals from the arm muscles were enhanced in the CN when a monkey voluntarily moved its arm, compared with when the robot moved it.
These studies established that the processing of signals coming from our body has already begun when signals reach the cuneate nucleus. But what are the brain cells and pathways that enable the CN’s selective enhancement of signals that matter and suppression of those that do not? In a third study, we took advantage of genetic and viral techniques to probe the nervous system of mice. With these tools, we could manipulate specific types of cells, turning them on or off by shining a laser at them. We paired these techniques with behavioral tasks: By training mice to pull a string or react to various textures for a reward, we tested how the activation or inactivation of specific neurons might affect a mouse’s ability to carry out dexterous tasks. This approach allowed us to first explore the functions of cells within the CN, revealing a specific set of neurons surrounding it that can suppress or enhance the passage of touch signals as they enter the brain. Then we applied similar techniques to examine how other higher brain regions may influence the CN’s activity. We discovered two different pathways from the cortex all the way down to the CN that govern how much information the cuneate allows to pass. In other words, the CN receives not only information from the body but also guidance from the cortex to help determine what signals are most relevant or important for an individual at any given moment.
Clearly, the cuneate nucleus is a far more interesting brain region than it has been given credit for. Our work helps clarify its function: to highlight certain signals and suppress others before passing them on to brain regions responsible for perception, motor control and higher cognitive functions. That important role may help to explain why the CN appears in a wide variety of mammals including mice and primates.
Though our work is far from finished, our results already have important implications for rehabilitation. Beyond the active tactile and muscle signals we were able to study, evidence suggests that the CN receives many more “dormant” inputs that may be important in recovery from neurological injury. Millions of people worldwide suffer from some form of limb dysfunction, such as paralysis or loss of feeling. With a better understanding of how sensory and motor signals support movement, doctors can eventually improve diagnosis and treatment of these conditions. For example, implanted electrodes could one day electrically activate the cuneate nucleus in people who have lost sensation in their limbs, potentially restoring the ability to perceive their body.
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