Scientists shed new light on walking

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Scientists shed new light on walking

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Researchers at the medical university Karolinska Institutet have created a

genetically modified mouse in which certain neurons can be activated by blue

light. Shining blue light on brainstems or spinal cords isolated from these mice

produces walking-like motor activity. The findings, which are published in the

scientific journal Nature Neuroscience, are of potential significance to the

recovery of walking after spinal cord injury.

" This new mouse model will impact the way in which future studies examining the

organization of neurons involved in walking are performed. We hope that our

findings can provide insight that eventually will contribute to treatments for

spinal cord injured patients " " , says Professor Ole Kiehn, who lead the study.

Excitatory neurons have been suggested to play an important role for the

initiation and maintenance of locomotion, or walking. However, this has not been

demonstrated directly. In order to test the hypothesis that activation of

excitatory neurons is essential to locomotion, a research team at the Department

of Neuroscience, Karolinska Institutet, created a genetically modified mouse

which expresses a light sensitive protein in excitatory neurons.

The light sensitive protein, Channelrhodopsin2 (ChR2), is normally found in

algae and activates the cell it is expressed in when exposed to blue light. ChR2

has previously been introduced into rodent cells by viral infection, but this

can be problematic due to exposure and replication demands. The researchers

circumvented the problems by creating the first genetically modified mouse to

successfully express ChR2 in a specific set of neurons.

By inserting ChR2 into nerve cells expressing Vglut2 - a transporter found in

most excitatory neurons in the brainstem and spinal cord as well as many

excitatory neurons in other regions of the brain - they created a Vglut2-ChR2

mouse . The reason for doing this was to be able to selectively activate

excitatory neurons in specific regions of the brainstem and spinal cord, as the

excitatory neurons are believed to be important for initiating locomotion, or

walking.

The researchers then recorded from motor nerves leaving the spinal cord. When

blue light was shined directly on the spinal cord, walking-like activity began

and was maintained for the duration of the light pulse. This proved that

activation of Vglut2-expressing excitatory neurons in the spinal cord is

sufficient for walking. Walking-like activity could also be initiated by

exposing the lower brainstem to blue light, demonstrating that excitatory cells

in the brainstem provide a sufficient 'go' signal to the spinal neurons involved

in walking.

All the experiments were made in vitro in the laboratory and not in living

animals.

Publication

Hägglund, Lotta Borgius, J Dougherty & Ole Kiehn

Activation of groups of excitatory neurons in the mammalian spinal cord or

hindbrain evokes locomotion

2010, doi:10.1038/nn.2482. Print issue 25 January 2010