Shedding light on the brain

 
 

With current treatments for epilepsy and Parkinson’s relying on surgery and drugs, Dwayne Byrne examines the advantages of Optogenetics in human healthcare

Since Watson and Crick sequenced the genome, genetics has dominated in biological research over the last number of decades, but with the mass availability of functional Magnetic Resonance Imaging (fMRI), neuroscience has shot forward dominating many of the headlines of the past decade or so. With the recent emergence of optogenetics, the knowledge gained through genetics can now be applied to helping neuroscientists discover the various brain-region functions never before understood.

Optogenetics is the combination of optical techniques and genetic modification which allows selected neurons to be activated on the flash of a light. A specific gene sequence is placed into the DNA of a neuron, which results in the expression of a protein facilitating the production of photoreceptive ion channels on the neuron’s surface. This channel, which responds by opening when a light is shone in the brain, allows ions to flow into the neuron causing an electrical signal to fire down along the cell and in turn activating a pathway in the brain.

Professor Miesenbӧck, University of Oxford, winner of the 2013 Brain Award for his work in optogenetics, was the first scientist to show optogenetic control in 2002. In this experiment, Miesenbӧck showed that particular groups of neurons could be precisely controlled, when light was shone on the brain of flies, whose skulls are thin enough for exterior light to penetrate and activate photosensitive receptors on their neurons without affecting neighbouring neurons. The beauty of optogenetics says Miesenbӧck is that “there are no high-tech gismos here just biology revealed through biology”.

This new neuroscience technique allows scientists to understand the complex pathways and systems involved in cognitive processes, especially those in humans. 2004 saw a major movement in Optogenetics, by Ed Boyden, a then graduate student and Karl Deisseroth, who was starting his own lab in Stanford University. The pair along with some collaborators, showed how they could use a protein, called channelrhodopsin-2, taken from green algae, to genetically modify neurons using a gene therapy vector (such as a virus) to produce the photoreceptive channel and activate it with the use of optical fibres implanted in the brain of mammals.

The activation of the channel causes it to change in conformation so that the channel will open allowing ions to flow in and an electrical charge flow down the neuronal cell, Boyden and Deisseroth showed that this process enabled them to control the excitatory and inhibitory synaptic transmission of the genetically modified neurons “yielding a widely applicable tool for neuroscientists and biomedical engineers”. Previous attempts at optogenetics had only been carried out in vitro, Boyden and Deisseroth were the first to carry out optogenetics experiments so precisely in living mammals.

Optogenetics enables scientists to control brain pathways, instead of just observing the activity and then ascribing function to certain types of neurons. By watching what the mammal does and seeing what neurons fire, scientists can now activate a specific area of the brain and then see what happens.

Optogenetics is currently being tested, tweaked and enhanced in labs worldwide, with hope that its international development will lead to the use of optogenetics in humans. With the potential to treat debilitating diseases like Parkinson’s and epilepsy this could be a major improvement on current treatment methods for neurological disorders, which only ease patient’s symptoms. Crucially, it allowed the control of neurons by shining light from an optical fibre without altering the normal function of these neurons when the blue light is not on.

Neurons are like minute computers which receive inputs from thousands of other neurons and then compute their own output. This is going on right now as you read this article, and will continue while you eat your dinner later, or even while you are sleeping. Cells such as basket cells, which are inhibitory (they prevent neighbouring cells from firing), are known to waste away in disorders like schizophrenia. Other neurons like pyramid cells are excitatory but are thought to be overactive in epilepsy. Current drugs alleviate symptoms but none have been able to cure any of the brain disorders that most commonly affect humans. Surgical treatments, like the removal of small parts of the brain in disorders like epilepsy, are not only irreversible but are not guaranteed to be 100% effective and are associated with major risk factors. Optogenetics is proving to be a potential treatment for epilepsy; “Inhibition of epileptiform activity has been demonstrated” claims Robert S. Fisher in his 2012 paper on treatments of epilepsy but, as with all forms of optogenetics, its “use in humans will require more work”.

Reward centres in the brain have been targeted for discovery as these centres which are thought to be major contributors in drug addiction, learning and depression. If these centres could be inhibited in drug addicts, the drugs they use would be less effective and thus less desirable for the addict. Boyden carried out experiments on the reward centres of mice, which demonstrated that the activation of pleasure centres within the brain can drive learning in mice. This may have a major application in those with learning difficulties, rewarding learning will make it less boring and hopefully less tedious.

It is still early days for the treatment of humans using optogenetics but this principle gives us great hope for possible future treatments of devastating disorders of the brain but may also allow scientific discoveries which may uncover some details about ourselves, our emotions and even our personalities that we have not understood to date.


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