Combining two light-based techniques has enabled researchers at University College London to both observe and control brain activity in mice. The approach involves simultaneous two-photon optogenetic activation of a red-shifted opsin in multiple neurons, as well as high-resolution brain network imaging via genetically encoded calcium indicator. “Combining reading and writing of activity in the same neurons in the intact brain could revolutionize how neuroscientists can interact with and understand brain activity,” said professor Dr. Michael Hausser. Six neurons arranged in the shape of a smiling face are simultaneously activated in the barrel cortex of a mouse brain. The response of those neurons is color coded in green, indicating the successful activation of this neuronal pattern of activity. Courtesy of Lloyd Russell, Hausser Lab, UCL. The researchers used a spatial light modulator to split up the activation signal into multiple beamlets that could be targeted to tens of neurons simultaneously. The team selected a group of neurons in the barrel cortex that are specifically responsive to the sensation of touch, reliably activating them while recording the flashes of activity in both the activated neurons and in hundreds of neighboring neurons. There was negligible optical cross-talk between the optogenetic activation and calcium imaging, the researchers said. Continued experimentation could help crack the “neural code” of sensory perception, and reveal how neural activity goes awry in neurological conditions such as autism and dementia, the researchers said. “We are very excited to use this technology to probe the basis of how groups of neurons, and ultimately the brain, stores and processes information from the world around us,” said research fellow Dr. Adam Packer. “This work provides a new way for neuroscientists to have a long-term and engaging conversation with the cerebral cortex in the brain of a mouse. Crucially, since the methods of both recording and activation rely on light, this technique is flexible and noninvasive.” Funding for the study came from the Wellcome Trust, the Gatsby Charitable Foundation, the European Commission, the European Molecular Biology Organization, the Medical Research Council and the European Research Council. The research was published in Nature Methods (doi:10.1038/nmeth.3217). For more information, visit www.ucl.ac.uk.