Reading and writing brain activity using light
Methods for precise stimulation of neurons are crucial for understanding how brain activity relates to behavior. Traditionally, neuroscientists placed electrodes in the brain to stimulate neurons. However, brain structures contain very diverse populations of cells, and electrodes activate any neuron in their vicinity, making it impossible to relate behavioural responses to stimulation of particular neurons. Optogenetics introduced the use of light for stimulating neurons, taking advantage of Channelrhodopsin. When exposed to blue light, the Channelrhodopsin protein opens a pore, allowing ions to enter and activate neurons to fire impulses. Neuroscientists can control the activity of restricted populations by placing Channelrhodopsin only in target neurons using genetic engineering.
Readings of activity are usually electrical. These have high definition but can only be targeted to 1-8 neurons at a time. However, the mammalian brain has billions of neurons working in coordinated groups to hold sensory information and execute behaviors. It would be advantageous to see the forest for the trees and track the activity of hundreds of individual neurons simultaneously. Impulse firing is accompanied by increases in intracellular calcium concentration. Activity can therefore be reported accurately by genetically-encoded calcium indicators, proteins that increase brightness whenever calcium concentration rises in a neuron. Brightness increases are detected by microscopes equipped with photon detectors and processed into images of neural activity, where active neurons appear brighter than silent ones. This technique, named “calcium imaging”, allows visualisation of activity in hundreds of neurons simultaneously.
A team at University College London has succeeded in combining optogenetic stimulation and calcium imaging. Using spatial light modulation, the authors split a laser beam into several “beamlets”, concurrently stimulating tens of neurons expressing channelrhodopsin. The effect of stimulating these neurons was monitored in hundreds of others using calcium imaging. Both optogenetic stimulation and calcium imaging took advantage of 2-photon technology, ensuring accuracy in three dimensions. This is a groundbreaking development, allowing scientists to potentially reveal neurons active during a particular behavior and then evoke this behavior by mimicking the same activity pattern artificially with optogenetics. This approach could greatly advance our understanding of the neural correlates of behavior, perception and cognition.
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