Because of the practical and ethical problems of experimenting on humans, it is very difficult to directly study the physiology of the intact human nervous system. However, there is one unusual (but safe) method for recording from single neurons in humans. This technique, called microneurography, requires impaling a peripheral nerve with a fine

tungsten electrode. The electrode is then finely repositioned until the spikes of an individual sensory axon are isolated. Microneurography was invented by Swedish neuroscientists Karl-Erik Hagbarth and Åke Vallbo, who boldly worked out the technical details by experimenting on themselves. The majority of microneurography studies are still performed by Hagbarth and Vallbo's successors in Sweden, presumably because of the technical challenges and obvious hazards of recording from human nerves.

One of the first applications of microneurography was to investigate mechanosensory neurons called muscle spindles. Deeply embedded within skeletal muscles, muscle spindles are proprioceptive sense organs that monitor the lengthening of surrounding muscle fibers. The muscle spindle itself contains specialized muscle cells, called intrafusal fibers. While skeletal muscles are controlled by alpha motor neurons, intrafusal fibers are innervated by a separate class of gamma motor neurons. The role of the gamma motor neurons is to adjust the mechanical sensitivity of the muscle spindle when the surrounding muscle contracts. Recording from human subjects, Vallbo discovered that alpha and gamma motor neurons often fire at the same time. Thus, when the primary muscle contracts and shortens, the intrafusal fibers also contract, increasing the tension on the muscle spindle organ. This phenomenon, called alpha–gamma co-activation, increases the ability of the muscle spindle to detect subsequent changes in muscle length.

In order to smoothly control the movement of joints, skeletal muscles often work together as antagonistic pairs: for example, when you point a finger, the extensor digitorum muscle contracts while its antagonistic partner, the flexor, relaxes. But are muscle spindles influenced by the activity of antagonistic muscles? In other words, does contraction of a flexor muscle affect the sensitivity of the extensor muscle spindle?

To answer this question, Michael Dimitriou, of Umeå University, Sweden, used microneurography to again record from human muscle spindle axons. After he isolated signals from a muscle spindle that controlled extension of a specific finger, Dimitriou asked his subjects to slowly and continuously wag that finger up and down. In some cases, an opposing force was applied to the finger, which required the subject to either increase or decrease muscle output. Although the finger movement kinematics remained constant across conditions, the activity in the flexor and extensor muscles varied, depending on the direction and amplitude of the applied external load. This allowed Dimitriou to compare trials in which the flexor muscle activity was the same, but the extensor muscle activity was variable, and vice versa.

Surprisingly, Dimitriou found that activity within an antagonistic muscle was negatively related to muscle spindle output. For example, extensor muscle spindles exhibited lower firing rates during contraction of antagonistic flexor muscles. This inhibitory relationship suggests that muscle spindle sensitivity actually reflects the balanced activity of both muscles within an antagonistic pair. Because antagonistic muscle pairs function together, adjusting spindle sensitivity based on the activity of both muscles may increase the ability of the muscle spindle to detect and encode muscle movements across a wide dynamic range.

How do signals from muscle spindles contribute to motor control? Many of our basic stretch reflexes, such as the knee-jerk response, result from direct muscle spindle feedback on to motor neurons. In the mouse, ablating muscle spindle neurons profoundly disrupts locomotor rhythms like walking and swimming. Finally, muscle spindle feedback might also be critical for the execution of fine motor skills, such as guiding a tungsten electrode into the radial nerve of a young Swedish student.

Human muscle spindle sensitivity reflects the balance of activity between antagonistic muscles
J. Neurosci.