Restoring normal function to damaged or diseased nervous tissue remains a major goal of both basic and clinical neuroscience research. Advances in genetic technologies now allow targeted control of neuronal activity in the mammalian nervous system, providing novel therapeutic avenues to repair or bypass faulty circuits. Here we review recent work published in the Journal of Neuroscience by Alilain et al., demonstrating the use of Channelrhodopsin-2 to restore breathing in rodent models of spinal cord injury.
"In SCI where one traumatic end result is diminished supraspinal input to motor neurons, we hypothesized that expression of ChR2 in spinal neurons and subsequent photostimulation might provide a powerful means to activate these otherwise quiescent cells and restore muscle activity. Therefore, in the C2 hemisection model, expression of ChR2 in the ipsilateral C3–C6 spinal cord and light stimulation could lead to a restoration of breathing activity in the fully adult animal (Alilain et al., 2008, for review please see Arenkiel and Peca, 2009). "
[Show abstract][Hide abstract] ABSTRACT: Loss of respiratory function is one of the leading causes of death following spinal cord injury. Because of this, much work has been done in studying ways to restore respiratory function following spinal cord injury (SCI) - including pharmacological and regeneration strategies. With the emergence of new and powerful tools from molecular neuroscience, new therapeutically relevant alternatives to these approaches have become available, including expression of light sensitive proteins called channelrhodopsins. In this article we briefly review the history of various attempts to restore breathing after C2 hemisection, and focus on our recent work using the activation of light sensitive channels to restore respiratory function after experimental SCI. We also discuss how such light-induced activity can help shed light on the inner workings of the central nervous system respiratory circuitry that controls diaphragmatic function.
[Show abstract][Hide abstract] ABSTRACT: Elucidation of the neural substrates underlying complex animal behaviors depends on precise activity control tools, as well as compatible readout methods. Recent developments in optogenetics have addressed this need, opening up new possibilities for systems neuroscience. Interrogation of even deep neural circuits can be conducted by directly probing the necessity and sufficiency of defined circuit elements with millisecond-scale, cell type-specific optical perturbations, coupled with suitable readouts such as electrophysiology, optical circuit dynamics measures and freely moving behavior in mammals. Here we collect in detail our strategies for delivering microbial opsin genes to deep mammalian brain structures in vivo, along with protocols for integrating the resulting optical control with compatible readouts (electrophysiological, optical and behavioral). The procedures described here, from initial virus preparation to systems-level functional readout, can be completed within 4-5 weeks. Together, these methods may help in providing circuit-level insight into the dynamics underlying complex mammalian behaviors in health and disease.
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