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Decision letter: Optogenetic feedback control of neural activity
Abstract: Cells called neurons use electrical signals to rapidly carry information around the body. When a neuron is activated, it generates (or ‘fires’) a short electrical impulse that travels along the cell to relay a message to other neurons, muscles or organs. Optogenetics is a technique that allows scientists to genetically modify neurons to produce proteins that make them light sensitive. One of the most commonly used light-sensitive proteins is called channelrhodopsin-2. It is activated by blue light and increases the electrical activity of neurons. Another protein is called halorhodopsin, which responds to yellow light and inhibits the firing of neurons. By shining light of particular colors onto neurons that produce these and other light-sensitive proteins, it is possible to manipulate the activity of large populations of neurons. Most previous optogenetic experiments have involved altering the activity of neurons and then observing the outcome at a later point in time. However, it would be very useful to be able to alter the amount of optical stimulation to achieve particular levels of neuron activity in real time. To achieve this, the level of neuron activity at any point in time would need to be quickly compared to the desired level, so that optogenetics could be used to increase or decrease the firing of neurons as appropriate. Newman et al. have now developed an optogenetic system called ‘optoclamp’ that can control the activity of neurons in real time. In neurons grown in cell culture, the optoclamp is able to hold the level of neuron activity at particular values for periods of time ranging from 60 seconds to 24 hours. It can be used to restore and maintain the baseline level of neuron activity in the presence of drugs that would otherwise produce large increases or decreases in the firing of neurons. Moreover, in anaesthetized rats, the optoclamp can prevent some neurons from being activated even when the rats' whiskers move, which would normally change their firing level. Newman et al.'s findings open the door to a new type of neuroscience experiment where it is possible to manipulate activity patterns as they are produced by the brain. This will help researchers to understand how particular patterns of brain activity are linked to learning, memory, and behavior.