Optogenetics reveal the organization of rhythmogenic locomotor networks
By using optogenetics — a method that involves the use of light to activate nerve cells — to stimulate excitatory and inhibitory neurons in the spinal cord, neuroscientists at Karolinska Institutet have managed to switch on and off neural circuits that control locomotion. The study, which is published in the scientific journal PNAS, shows that the basic structure underlying the locomotor network in mammals has a distributed organization with many intrinsically rhythmogenic modules. The results provide deeper insight into how networks of nerve cells cooperate to generate complex movements.
Optogenetics uses genetic techniques to express light sensitive channels from unicellular organisms in specific populations of cells in multicellular organisms to be able to turn on and off the activity of these cells with light. The most widely used channel, Channelrhodopsin-2 (ChR2), when expressed in neurons, can make the neurons excitable when they are illuminated by blue light. The channel that governs the process of light-induced deactivation of neurons is called Halorhodopsin (HR). Optogenetics is now widely used in neuroscience to gain bi-directional control of neuronal activity in a cell specific way.
Professor Ole Kiehn's research group at the Department of Neuroscience, Karolinska Institutet was one of the first to produce a genetically modified mouse in which ChR2 was found in molecularly defined groups of cells. In a study published in 2010 in Nature Neuroscience the researchers showed that light-activation of excitatory neurons expressing ChR2 in the spinal cord was able to activate locomotion.
"We've now taken this work further," says the study's first author Martin Hägglund. "In the study we've just published, we used several different optogenetic methods that enabled us to activate or inactivate groups of excitatory or inhibitory neurons by shining light on them."
The experiments in the present study were conducted in vitro. Using ChR2 and HR, the researchers were able to show that the networks of cells that control locomotion are formed of clusters, or modules, of neurons that control individual muscles. These modules are like building blocks which interconnect with each other during locomotion to generate coordinated activity. The conclusions of the study show how molecularly defined groups of neurons produce and control movements.
The study was financed by grants from the Söderberg Foundation, the Swedish Research Council, Karolinska Institutet and the European Research Council (ERC).
Publication
Optogenetic dissection reveals multiple rhythmogenic modules underlying locomotion.
Proc. Natl. Acad. Sci. U.S.A. 2013 Jul;110(28):11589-94