Optogenetics is a technique used for the study of neural circuits in the brain. It is a branch of biotechnology that combines genetics and optical techniques to conceive and control a specific neural circuit in a living human brain.
The opsin technology was first developed from the concept of channelrhodopsin; a light-stimulated ion channel present in green algae Chlamydomonas reinhardtii, and later a group of neuroscientists who discovered optogenetics. It is divided into two fields as effector and sensor optogenetics, where the effectors deal with the manifestation of neural circuits and the sensors are used to manage the neural circuits.
The green fluorescent protein (GFP) technique and the other component devices utilizing multiple genes to produce photo-sensitive action potentials are grouped under optogenetics technology. Investigation on the efficiency of the technology with other tools and the study for further improvement of existing drugs and related diseases are carried out extensively to expand its application in treatment strategies for human.
A brief origin of optogenetics
Francis Crick, co-discoverer of DNA structure, recommended an idea about the possibility of controlling a target neuron using light. Over the years, much research on the eye was conducted to provide related ideas. Photoreceptor cells are specialized types of neuron cells in the retina which are responsive to light, and they convert light energy into chemical signals that alter neuronal action to stimulate biological processes. With the results from the experiments, the focus on controlling the neuronal activity has increased.
It is found that certain microbial organisms are able to produce light-gated proteins which can control the movement of ions through the plasma membrane. Researchers found that bacteriorhodopsin is believed to be an ion transporter which is rapidly photo activated by visible lights. Later, halorhodopsin and channelrhodopsin discovered in microorganisms were photo-sensitive proteins expressed specific genes.
The introduction of the microbial opsin gene into the neuronal cell has shown it to be actively sensitive to light. After several studies with channelrhodopsin and halorhodopsin, it has proven that they are capable of switching on and off the neurons. The naturally occurring retinoid tissues called all-trans retinal—a principle cofactor involved in microbial opsin control—exhibited that optogenetic approach is possible in mammalian brain without any damage.
The working of optogenetics
In optogenetics, the desired light-sensitive ion channels (GEP, channelrhodopsin, halorhodopsin, etc.) are delivered into a target gene through viral vectors. On illumination, these light-sensitive ion channels after transduction either switch on or off accordingly to study the disease pattern and efficiency of the treatment provided. Using this technique, even the more complex tissues of the living brain are easily studied. For instance, on experimenting in a mouse, it utilizes “light pipes” to deliver light to specified regions of the brain, which stimulates olfactory nerves to turn on the motor center to activate physical activity.
Studies have previously shown that transfecting channelrhodopsin gene into retinal cells re-establishes the light responsiveness in photoreceptor-lacking mice. Finally, this technique is an effective and advantageous method in treating blindness caused by macular deterioration and other disorders in humans than harmful therapeutic approaches.
Enhancement of the technique
Despite the latest invention of optogenetic technology to monitor the neurons activity in the brain, researchers have made outstanding developments in this technique. It has helped in the study of the performances of the brain circuit and registering the neurons activity linking the two hemispheres of the cerebrum.
Additionally, optogenetics can be applied in the study of numerous disorders that arise in the brain. In addition, this process has been carried out utilizing channelrhodopsin and halorhodopsin proteins, which helps in studying the brain stimulation through distinguishing neural circuits. Furthermore, optogenetics are used in some diseases as Parkinson’s disease to enhance the efficiency of the treatment.
Still much effort has been made currently to improve the optogenetic techniques. Although viral vectors are employed, delivering rhodopsin genes into target neurons is effectual and clinically possible; it is still an arduous procedure to improve constructs that make the most of the efficacy of gene deliver and expression.
Even if the naturally occurring ion channels rhodopsin and halorhodopsin perform the best, the genetically improved version of these proteins will increase their response to light. Advanced light delivery system is needed for better precision and effectiveness of the technique. In this technique, light-emitting diodes and infrared illumination systems are also used to efficiently image the different targets of the brain and to go through deep into the brain intensively.
Through many investigations, it is evident that optogenetics provide great scope for fundamental neuroscience research and proposes refined neurological treatment approaches in the future. Optogenetics act as a bridge between the complex cellular neurophysiology and diverse molecular systematic function. In addition, it provides answers for many experimental mysteries in neuroscience. Although it faces many challenges and risks in biomedical applications, much research has been carried out to improve its efficiency in therapeutic strategies.
Reviewed by Afsaneh Khetrapal BSc (Hons)