Methods based on genetically encoded molecular constructs such as antisense knockdown and RNA interference, which alter the expression of target genes, are widely used for analyzing the functions of the proteins encoded by these genes; they are also used in medical practice. Use of these methods has established, for example, that even short-term decreases in the expression of one of the noradrenaline receptors during the critical period of brain development leaves a long-lasting trace at the neurochemical and behavioral levels in subsequent life. Delivery to cells of viral constructs encoding any protein influencing cell function or small hairpin RNA (shRNA), which decrease the expression of a target gene, are also used in neurobiology. Optogenetics and chemogenetics provide clear demonstrations of the power of genetically encoded tools in studies of the central nervous system and are tools potentially suitable for controlling brain cell activity with therapeutic purposes. Both approaches are realized via expression in the target cell type of receptors novel for the organism and reacting to light of a specific wavelength or a chemical ligand molecule foreign to the organism. These approaches allow the functional consequences of changes in the activity of a specific population of neurons to be studied, and this has led to significant progress in deciphering the mechanisms of the central regulation of behavior. Thus, optogenetic studies have shown that activation of glutamatergic neurons in the dorsal hippocampus induce depression-like behavior, while the antidepressant effect of ketamine on this behavior is mediated by a direct action of this drug on NMDA receptors. Genome editing and gene expression control methods developed in recent years using bacterial CRISPR/Cas systems have already been used to study brain function. There are now optimistic expectations for the medical use of potential methods of opto- and chemogenetics, as well as CRISPR/Cas technologies, developed in model systems.
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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 105, No. 11, pp. 1381–1391, November, 2019.
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Dygalo, N.N. Investigation of Brain Functions Using Genetically Encoded Tools. Neurosci Behav Physi 50, 1051–1056 (2020). https://doi.org/10.1007/s11055-020-01004-y
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DOI: https://doi.org/10.1007/s11055-020-01004-y