Abstract
Many methods are available for the manipulation of brain function and behavior. From pharmacological tools through electrophysiological techniques to neuroanatomical procedures, an arsenal of approaches has been successfully utilized to answer the question of how the brain works and what may be behind its dysfunction in human disorders. Why do many scientists prefer to use genetics then? There may be two principally different reasons for this choice: one relates to evolution, the other to practical or mechanistic points. Ultimately, all behavioral features of an organism, and thus all functional aspects of its brain, must pass the test of natural selection. Natural selection operates at the level of genes. In other words, albeit often complex and difficult to disentangle, the effects of genes on brain function and behavior is not questionable. The second reason is more practical, and concerns how efficiently a biologist can answer mechanistic questions. The cause of human CNS disorders is often multifaceted, and is usually expected to involve numerous unknown environmental factors. Simply put, the number of such environmental factors could be staggering, whereas the number of genes one can manipulate is only about 25,000. Identifying a gene is also much simpler than identifying environmental agents possibly involved in brain dysfunction. A good example for this reasoning is the discovery of the involvement of Amyloid Precursor Protein (APP) misprocessing in Alzheimer's Disease. Only <5% of Alzheimer cases are familial, i.e., heritable, yet it was the discovery, for example, of APP mutations and the mutations in APP processing enzymes that propelled the understanding of the disease forward. Another mechanistic reason why genetic manipulation is often preferred to other methods is the specificity of the former. Modern recombinant DNA methods allow one to precisely silence a single gene, or change its expression in a brain region specific manner, or even modulate neuronal function in particular circuits and at particular time points. This level of control, temporal and spatial resolution, as well as target specificity are often not achievable with methods other than genetics. The current special topic will present numerous such genetic techniques, the first, and perhaps the most famous of which being homologous recombination-based gene targeting in embryonic stem cells.
Highlights
From pharmacological tools through electrophysiological techniques to neuroanatomical procedures, an arsenal of approaches has been successfully utilized to answer the question of how the brain works and what may be behind its dysfunction in human disorders
This special topic presents a collection of papers that focus on how gene targeting has been utilized in neurobiology, i.e., in the analysis of the biological mechanisms of brain function and behavior
The Clustered regularly-interspaced short palindromic repeats (CRISPR) and CRISPR associated protein 9 (Cas9) system enables the researcher to create double stranded cuts at pre-specified nucleotide sequences of choice (Walters et al.). Both the Transcription activator-like effector nuclease (TALEN) and the CRISPR/Cas9 system can be employed in species other than the mouse or the rat, the two laboratory model organisms to which ES cell based genetargeting methods of the past were restricted
Summary
Many methods are available for the manipulation of brain function and behavior. From pharmacological tools through electrophysiological techniques to neuroanatomical procedures, an arsenal of approaches has been successfully utilized to answer the question of how the brain works and what may be behind its dysfunction in human disorders. Another mechanistic reason why genetic manipulation is often preferred to other methods is the specificity of the former.
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