Abstract
Methods based on genetically-encoded molecular constructs, such as antisense-knockdown and RNA interference that alter the expression of target genes, are widely used to analyze the function of proteins encoded by these genes, and also find application in medical practice. Using these methods, for example, we found that even a short-term decrease in the expression of one of the norepinephrine receptors during the critical period of brain development leaves a long-lasting impact on the neurochemical and behavioral traits in later life. Delivery into the brain cells of viral vectors encoding any proteins that affect cell function or small hairpin RNA (shRNA) that reduce the expression of the target gene, also finds use in neurobiology. A vivid manifestation of the power of genetically encoded instruments in studies of the central nervous system, instruments potentially suitable for controlling the activity of brain cells for therapeutic purposes are optogenetics and chemogenetics. Both approaches realized by expressing receptors in the desired cell type that are new to the body, reacting to light of a certain wavelength or a chemical ligand unusual for the body. These approaches make it possible to evaluate the functional consequences of changes in the activity of a specific population of neurons, which, for example, has provided significant progress in deciphering the mechanisms of central regulation of behavior. For example, using optogenetics, we found that the activation of glutamatergic neurons of the dorsal hippocampus induces a depressive-like behavior, and the antidepressant effect of ketamine on this behavior produced by its direct action on the NMDA receptors. Developed in the past few years, genome editing and gene expression management techniques based on bacterial CRISPR/Cas systems already used to study brain function. At present, possible applications of opto- and chemogenetics, as well as CRISPR/Cas technologies in medicine are being developed on model objects with optimistic expectations.
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