Central pattern generators (CPGs) are neural networks in the spinal cord that generate the rhythmic patterns observed in many complex movements like chewing, breathing and walking. Within CPGs excitatory glutamatergic neurons have been implicated in generating these rhythmic patterns, and glutamatergic neurons in the hindbrain region that extend into the spinal cord are thought to be important in initiating locomotion. However, direct evidence of the involvement of these neurons in such activities has been hard to obtain.

In a Nature Neuroscience paper, Hägglund et al. present evidence using a transgenic mouse model that these excitatory neurons are indeed involved in rhythmic pattern generation and initiating locomotion. Their mouse model provides a powerful tool for studying the neural networks involved in movement. Understanding the biology of normal movement in mammals is a significant first step to better therapeutics for individuals suffering from spinal cord injuries that impair locomotion.

The researchers created a transgenic mouse that expressed the algal cation channel Channel-rhodopsin-2 (ChR2) under control of the Vglut2 promoter in glutamatergic neurons in mouse hindbrain and spinal cord. The channel opens in response to blue light, and the neuronal populations expressing the construct (Vglut2-ChR2-YFP) can be activated using blue light, without affecting endogenous Vglut2 activity.

All experiments were carried out in vitro, not on intact animals, but the authors were able to selectively activate glutamatergic neurons in the lumbar locomotor region of the spinal cord and initiate and maintain rhythmic neural outputs, with appropriate left-right and flexor-extensor alternation. Additionally, when they activated glutamatergic neurons in the hindbrain, those neurons provided a direct command that could activate the spinal locomotor network.

These studies do not rule out the possibility that other neurons may be involved in complex motor activities like walking, but they do demonstrate a direct role of excitatory glutamatergic neurons in CPG function. Complex motor functions like walking not only require the rhythmic patterns of neural activity that allow one foot to move in front of the other, but input from a variety of other stimuli to maintain balance and direction, for instance.

This mouse model will perhaps help to shed a little more light on the neural paths involved in complex motor activities like walking.

Hägglund, M., Borgius, L., Dougherty, K., & Kiehn, O. (2010). Activation of groups of excitatory neurons in the mammalian spinal cord or hindbrain evokes locomotion Nature Neuroscience, 13 (2), 246-252 DOI: 10.1038/nn.2482

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Michele Arduengo

Supervisor, Digital Marketing Program Group at Promega Corporation

Michele earned her B.A. in biology at Wesleyan College in Macon, GA, and her PhD through the BCDB Program at Emory University in Atlanta, GA where she studied cell differentiation in the model system C. elegans. She taught on the faculty of Morningside University in Sioux City, IA, and continues to mentor science writers and teachers through volunteer activities. Michele manages the digital marketing program team at Promega.

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