What do single cell green algae have to do with the state of the art of neuroscience?

Well, a lot actually!  Green algae, or Chlamydomonas reinhardtii to be formal, are the unicellular organisms with a unique trait that has been helping make huge advances in modern neuroscience in only the past eight years.  In their natural environment, these little organisms use an “eye spot” located inside the cell to detect light and to swim toward it (phototaxis).  Researchers have been studying these little critters for years and discovered the algae use a unique photosensitive ion channel that converts a light signal into a voltage change that provides information to the algae.

In 2005, a paper published by Edward Boyden, Ph.D. (MIT) and Karl Deisseroth, M.D., Ph.D. (Stanford) demonstrated that this light sensitive channel, named channelrhodopsin-2, could be introduced into neurons using engineered viruses and was capable of activating the neurons in the presence of blue light!  The authors reasoned that since neurons were essentially little batteries that were capable of firing action potentials, they might be able to control the neurons with an ion channel that is able to change the voltage across the membrane.  In their paper, they show that channelrhodopsin is not only capable of depolarizing neurons, but also can precisely control the timing of a neuron’s action potential.

The structure of channelrhodopsin and how it can be used to control neuronal activity is shown in Figure 1 below.  Blue light pulses activate the protein and change the voltage across the membrane by allowing sodium ions (Na⁺) to flow into the cell and potassium ions (K⁺) to flow out.  If this voltage change is able to trigger an action potential, then the neuron communicates with other neurons to which it is connected.  Figure 2 shows a single neuron firing action potentials in response to blue light!  This groundbreaking paper opened up a whole new field of neuroscience, called “optogenetics”.  Since this groundbreaking discovery, over 300 papers have been published using channelrhodopsin to activate neurons in specific parts of the brain in order to ask specific scientific questions about how it operates.

In a later paper, published in 2007, Dr. Deisseroth’s lab described another light-activated protein called halorhodopsin that was effectively able to suppress neuronal activity!  This protein responds to yellow light and pumps chloride ions (Cl^–) into the neuron, which helps hyperpolarize the membrane (Figure 3).  When Dr. Deisseroth’s lab introduced this protein in neurons, it was able to suppress neuronal activity!  In Figure 4, the spontaneous action potentials of a single neuron are suppressed when yellow light is turned on.  Importantly, once the yellow light is shut off, the cell begins to fire normally!  Used together, channelrhodopsin and halorhodopsin are able to both activate and suppress the activity of neurons in specific regions of the brain.

These novel scientific tools have allowed scientists to ask new and exciting questions about how the brain works, but they may also allow researchers and doctors to treat neurological diseases in the future!  There are a plethora of neurological diseases in which certain groups of neurons are either more or less active than they should be.  Therefore, it may be possible to use engineered viruses to put channelrhodopsin or halorhodopsin into the brains of humans with diseases.

In the article discussed this past Monday, researches at the University of California, Irvine tested the possibility of using channelrhodopsin and halorhodopsin to control seizures in epileptic mice!  Although these potential therapies are still years away from being used in humans, researchers are already demonstrating that optogenetics tools may be effective treatments for neurological diseases as well as powerful tools for neuroscience research!

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Written by Ryan Jones.

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