Ushering the future of psychiatric research with optogenetics

Jan 30, 2023 · 4 min read

Rene Decartes, once said that the mind exists separate from the body back in the 16th century. This may be why psychiatric disorders are among the most difficult to both diagnose and to treat. Many other disorders can usually be tested or imaged, whilst most psychiatric conditions still rely on individual consultations rather than examining the brain directly. To allow for a better understanding of the brain’s circuitry especially when disrupted during psychiatric disorders, Francis Crick - one of the founders of the structure of the DNA molecule suggested that neuroscience needed to have a switch that could turn specific neurons on or off.

In the brain, the electrical activity of cells called neurons and how they project to their nearest neighbours, help regulate behaviour. When there are deficits in these activities, we think they are the root cause of various psychiatric disorders. However, the exact details behind how these neural activities work has eluded scientists for many years. Lately, a promising technology called optogenetics may help us understand the pathophysiology behind many disorders.

How does optogenetics work?

Optogenetics uses molecules that convert light into electricity inserted into neurons through novel gene-therapy techniques (1). Once in place, researchers can shine light on neurons, letting them switch each neuron effectively on or off. This can let researchers look at what the end result of behaviours is if there are certain neurons turned on, and conversely which neurons are essential, such that they would lead to disorders if turned off. The promise of this technology is the precision at which researchers are able to target individual neurons.

Finding the aetiology of anxiety

We live in a time where mental illness is on the rise, with nearly 1 in 5 individuals suffering from a mental illness (2). But like many disorders, the underlying mechanism behind even the most common illnesses such as anxiety are unclear.

While we know that fear and anxiety is primarily controlled by the amygdala, we were unclear of the details until a certain experiment with mice in 2011 showed that when the bed nucleus of the stria terminalis region of the amygdala was involved with anxiety-related behaviours (3). For example, when optogenetics was used to stimulate these neurons, the mice were calmer, and when inhibited they displayed anxious behaviour as well as a higher respiratory rate.

Where are we currently at with optogenetics?

Currently, optogenetics is still used in ongoing research into other mental disorders such as depression, but also relatively rare disorders such as schizophrenia and bipolar disorder. However, many of these studies are based on mouse models and have yet to be translated to humans. Thus, any inferences made are contingent on the evolutionary similarity between humans and mice.

The major reason why, is primarily because in order to stimulate neurons, gene therapy must be used to transfer genes encoding photosynthetic machinery from algae, fungi or bacteria. Gene therapy, whilst gaining momentum, is still in its infancy in terms of regulatory development. Furthermore, we are still unaware of the consequences of injecting foreign bodies such as the effect on the immune system (4).

How can we diagnose and treat people better using optogenetics?

However, the future does look promising with optogenetics. We know that many psychotropic drugs that are used to manage psychiatric disorders work by modulating the level of neurotransmitters which in turn modulate the electrical activity within the brain. However, these drugs rarely are specific and can affect the biochemistry of various regions within the brain, in turn potentially a lack of effectiveness. Through optogenetics, we can hone in on the specific neurons we know cause the disorder and target molecules within those circuits leading to better drugs that are specific to the patient, potentially reducing side effects (4).

Alternatively, we can use optogenetics directly through stimulating the specific neurons, in situ, or in place, where light can be used directly to stimulate a specific subset of neurons as a part of a therapy. However, the flexibility of optogenetics means that the neuron doesn’t necessarily have to be in the brain, but other peripheral nerves such as within muscles. Despite initially being positioned to understand the brain, optogenetics could be used to help muscles contract in disorders such as cerebral palsy (5).

Optogenetics has come light years since Prof. Deisseroth at Stanford trialled the idea that opsins from green algae (aka pond scum) are at the heart of optogenetic technology to turn on and off neurons. We are still uncovering the various uses to apply optogenetics not only to understand the basis of psychiatric disorders but also treating them (5).

Ushering the future of psychiatric research with optogenetics

How does optogenetics work?

Finding the aetiology of anxiety

Where are we currently at with optogenetics?

How can we diagnose and treat people better using optogenetics?

References