Optogenetics is the science of using light sensitive microbial ion channels to manipulate neural activity in higher organisms. Examples of the microbial opsins which have been adapted to optogenetics are the depolarizing Na/K transporter Channelrhodopsin (e.g. ChR2), the hyperpolarizing chloride pump Halorhodopsin (e.g. NpHR3.0), and the hyperpolarizing proton pump Arch. Optogenetic channels have been expressed using electroporation, viral vectors, and targeted transgenesis in mice. Once expressed, the activity of the channel, and the neuron in which it is expressed, can be manipulated using light delivered by an LED or laser. Although still in its infancy, optogenetics has proven remarkably versatile, allowing manipulation of single neurons and groups of neurons both in vitro and in vivo.
One of the major challenges of applying optogenetics in the rodent brain is obtaining specific expression of the channel in the neurons of interest. This is especially important in deep brain structures, where many cell types (GABAergic, glutamatergic, monoaminergic, etc.) may be found within a small anatomical area. Although in some cases viral expression can be manipulated with specific promoter sequences, usually viral vectors do not discriminate between different cell types within a brain region. Our ability to achieve precisely targeted expression of optogenetic channels has been greatly advanced by a recent collaboration between investigators at CIBR and colleagues at the Allen Institute for Brain Science in which we have demonstrated a “combinatorial” transgenic approach to optogenetics. In this system, mouse lines expressing Cre recombinase in the neuron of interest are crossed with lines which conditionally express ChR2, NpHR3.0 or Arch from a modified Rosa26 locus. In this way, excitatory and inhibitory channels can potentially be expressed in any neuron that can be defined by a specific gene that can be used to target Cre.
- Eric Turner
- Nino Ramirez
- John Welsh
- Optogenetic approach to the function of the habenulopeduncular pathway
- Optogentic Control of Mitochondrial Function
- Optogenetics in Cerebellar Systems