Optogenetics has greatly enlarged the scope of neuroscience by making possible the study of particular neural circuit components in both normal and diseased states.
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Optogenetics has helped scientists and doctors understand neural circuit behavior and responses in a variety of conditions such as mood disorders, addiction, Parkinson’s disease, obsessive compulsive disorder, social behavior, and reward, and many more.
In the last decade a number of optogenetic tools have been developed both by discovery and engineering; we now have a battery of opsins that can be used to manipulate (both stimulate or inhibit) neuronal activity as well as certain intracellular signaling cascades.
The trend now is to refine combination approaches (e.g., integration of optogenetic control with imaging of genetically defined neural populations) so as achieve better insights into neuronal circuit behavior in normal persons and their dysfunction in psychiatric disease states.
Optogenetics for treatment of depressive disorder
Depression is the most common life-threatening mental disorder. Although the study on depression was carried out for a long term, the fundamental mechanisms are mostly unrevealed. Antidepressants, that are common, are very effective in a few patients but it shows the side effects in noradrenergic and serotonin neurotransmission in some people with 28% efficacy.
Nearly 30%–40% of the people are resistant to treatment for depression. These patients can be treated with optogenetics. The changes in activity of neurons cause panic, distress, depression with regard to positive affect, and animals to encounter depressive disorders.
The development in methods that are used for documenting and managing neural activity in the reward system of the brain has led to clear understanding of the neuronal circuits that reveal various symptoms like anhedonia. This enables to a better treatment for depression.
Likewise, the basolateral amygdala neuron or their extension into the circuits in central amygdala was detected by optogenetics to reveal the characteristics of anxiety, a frequent symptom of depression, and to regulate conditional fear. The optogenetic technique helps in target-specific identification in a circuit and manipulates the target to fix the dysfunction.
To analyze the key aspects of depressive disorders, the optogenetic techniques were used focusing dopaminergic neurons of VTA. The other brain components such as nucleus accumbens, hippocampus, PFC, and amygdala also have protrusions of the VTA region which show the changes in the structure of neurons in patients with depression.
Using this technique, the dopaminergic neurons of VTA expressing channel rhodopsin in two models of depression are stimulated, and as a result, an instant change in behavioral responses was observed.
The sucrose consumption test and forced swim test were carried out in CMUS-induced depression mice which showed that the stability on psychological emotions has been recovered on pulse-phase stimulation and enhanced the depressive-like state on inhibition.
Collectively, the study on chronic stress-induced and depression-induced signaling tracts and neuronal circuits helps to understand and to develop effective therapeutic approaches for depression. Employing necessary temporal outcomes and renowned optogenetic methods is the perfect approach for these experiments.
Optogenetic therapy in SCI
In clinical neurology, optogenetics can be used for treating spinal cord injuries (SCIs). Traditionally, electricity is the most prevalent stimulus which is used to stimulate the neuromuscular elements. One of the successful techniques involving electric pulses is an FES that helps to restore or improve the paralyzed muscles that assist in breathing, the upper and lower limb mechanism, and the bowel and bladder regulation.
In spite of its justified potency, the inability of activation control narrowed down the combination of FES techniques. This inability can be overcome by optogenetics which has accurate and continuous time period resolution.
Pitfalls in applications
There are some aspects to consider while planning an optogenetics experiment.
- Delivery of light for opsin activation may not be uniform, and so the response of the target neuron population may not be uniform.
- Optogenetic stimulation can push some of the cells to a state not within their normal physiological range, thereby potentially leading to result in consequences.
- Optogenetic stimulation tends to synchronize the activity of all resident cells in the target population, which can lead to the loss of individual-specific neuronal firing patterns in that population.
- Optogenetic tools have a tendency to categorically influence all cells with a genetically defined characteristic; they cannot, therefore, modulate specific subsets of the target population.
- Optogenetic tools can sometimes lead to direct illumination and subsequent stimulation of axonal membranes, in turn causing activation of neuronal cell bodies and even other regions of the brain via activated collaterals (antidromic activation). When such things happen, different circuits are activated, reducing the specificity of the manipulation; inhibitory opsins may sometimes be used to avoid such complications.
- The opsin protein themselves have the potential to affect the functions of the intrinsic cellular machinery, causing disruption of structures such ion channels and pumps.
For all these reasons, optogenetic experiments have to be planned with a careful consideration of all the possibilities.
Reviewed by Afsaneh Khetrapal Bsc (Hons)