Exciting New Technique to Simultaneously Read and Write Brain Activity

A team at the University College London (UCL) have developed a “revolutionary” new technique that allows us to simultaneously record and alter brain signals.


The new all-optical method, published in Nature Methods by Adam Packer and his colleagues at UCL, involves the use of two cutting-edge techniques: optogenetics and calcium imaging. In combing these techniques, researchers can not only engineer neural cells to visibly light up when they are activated, but they can also manipulate the activity of these same cells using light pulses – allowing the simultaneous observation and control of brain activity.

Establishing a cause and effect relationship between certain behaviour and certain brain activity is notoriously difficult using the traditional neuroscientific methods such as magnetic resonance imaging (MRI) or electroencephalography (EEG). In recent years, researchers sought to tackle this issue with the advent of optogenetics, which essentially allows researchers to ‘write’ brain activity. Optogenetics is a technique whereby mice are genetically engineered to express certain proteins (channelrhodopsins), which render specified neurons to be light sensitive. By forging a “window” in the skull of an animal, light pulses can be delivered on a millisecond-by-millisecond basis to activate or deactivate these specific neurons.


In order to ‘read’ brain activity, a technique is used here called calcium imaging. The concentration of calcium ions within a neuron immediately surge when it becomes active. Using fluorescent dyes, these surges in calcium can be detected and act as a sign of that neuron being active. Therefore, researchers can effectively ‘read’ the activity of an entire cell population within a live (animal) brain based on the calcium signals.


Through combining these methods, Packer and his colleagues were able to optogenetically activate specific cells while also using high-speed calcium imaging to visualise how they and other cells in the population react to stimulation, through transparent ‘windows’ in the animals’ skulls. This new technique can be applied over weeks or even months in live animals, allowing us to gather information about the link between brain and behaviour and decipher the corresponding neural codes to an unprecedented degree.


According to Professor Michael Hauser (a senior author on the study), the consequence of this is best understood in terms of having a conversation: “One of the best things about having an extended conversation with someone is that you can really get to know them. With time, their responses can give you a feel for the key questions to ask in order to understand their character. Just as we combine specific words into sentences that elicit a reply from someone we talk to, we used light to activate specific combinations of nerve cells in the intact brain and record how the other cells respond. In this way, we hope to be able to ask the brain questions and, from its answers, better understand how it works.”


Hauser suggests that this technique could revolutionise the way in which we study the brain and it is hard to disagree. The scope of its use extends from cracking neural codes associated with behaviour to aiding our understanding of how neural activity falters in neurological disorders. As the popularity of this technique grows, so will the sophistication in which it is utilised and hopefully we will see an exponential rise in our understanding of the brain.


Packer, A. M., et al. (2014). Simultaneous all-optical manipulation and recording of neural circuit activity with cellular resolution in vivo. Nat. Methods, Advance online publication. DOI: 10.1038/Nmeth.3217

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