Mar. 31, 2014

Two-Photon Microscopy: Muscle-Controlling Neurons Know When They Mess Up

  • A two-photon microscopy image of a mouse´s Purkinje cells. (Photo: Andrea Giovannucci)A two-photon microscopy image of a mouse´s Purkinje cells. (Photo: Andrea Giovannucci)

Whether it is playing a piano sonata or acing a tennis serve, the brain needs to orchestrate precise, coordinated control over the body's many muscles. Moreover, there needs to be some kind of feedback from the senses should any of those movements go wrong. Neurons that coordinate those movements, known as Purkinje cells, and ones that provide feedback when there is an error or unexpected sensation, known as climbing fibers, work in close concert to fine-tune motor control.

A team of researchers from the University of Pennsylvania and Princeton University has now begun to unravel the decades-spanning paradox concerning how this feedback system works.

At the heart of this puzzle is the fact that while climbing fibers send signals to Purkinje cells when there is an error to report, they also fire spontaneously, about once a second. There did not seem to be any mechanism by which individual Purkinje cells could detect a legitimate error signal from within this deafening noise of random firing.

Using a microscopy technique that allowed the researchers to directly visualize the chemical signaling occurring between the climbing fibers and Purkinje cells of live, active mice, the Penn team has for the first time shown that there is a measurable difference between "true" and "false" signals.

This knowledge will be fundamental to future studies of fine motor control, particularly with regards to how movements can be improved with practice.

The research was conducted by Javier Medina, assistant professor in the Department of Psychology in Penn's School of Arts and Sciences, and Farzaneh Najafi, a graduate student in the Department of Biology. They collaborated with postdoctoral fellow Andrea Giovannucci and associate professor Samuel S. H. Wang of Princeton University.

Original publication:
Farzaneh Najafi, Andrea Giovannucci, Samuel S-H Wang, Javier F Medina: Sensory-Driven Enhancement of Calcium Signals in Individual Purkinje Cell Dendrites of Awake Mice, Cell Reports, Volume 6, Issue 5, 792-798 (2014)

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