In the fascinating field of neuroscience, the study of brain neurons holds paramount importance. Understanding the intricate mechanisms underlying neuronal function is a fundamental pursuit in deciphering the mysteries of the human brain. To this end, researchers and scientists have been employing innovative techniques, including chemical genetics, to unravel the complexities of brain neuron detection.
At Creative Biolabs, we delve into the captivating realm of brain neuron detection using chemical genetics, shedding light on the significance of this technique and its potential applications in unraveling the intricacies of the brain.
Principles of Chemical Genetics Technology
Chemical genetics technology is to use the disciplinary principles of chemistry and genetics to genetically engineer some macromolecular protein receptors so that they can interact with some artificially modified small-molecule compounds, and then control the activity of the macromolecular protein receptors and influence the downstream intracellular physiological responses such as cell signaling pathways to achieve the experimental purpose of manipulating cellular activity.
Therefore, chemical genetics techniques can be used for drug target screening discovery and related drug development, in addition to revealing the basic cellular activity patterns.
Chemical Genetics VS Optogenetics
As two commonly used techniques in neuroscience research, optogenetics and chemical genetics have their own distinctive features. Before conducting formal experiments, it is necessary to clarify the differences between them and their own advantages and disadvantages in order to better select the appropriate operating techniques and reap good experimental results.
Time & Space
Milliseconds, even sub-milliseconds
Up to single cell level
Hourly, can affect neuronal activity for hours
Up to a specific type level
Real-time regulation of cell activity, more flexible
Cannot do real-time regulation of cell activity
High cellular energy consumption and light effects can damage cells
Do not affect normal cellular activity
Highly traumatic, prevent normal animal movement
Non-invasive, little disturbance to animals
Scientists have developed designer receptors exclusively activated by designer drugs (READDs) by using pharmacologically inert, drug-like small molecule compounds to activate GPCRs. CNO, a small molecule compound with good ability to penetrate the central nervous system, has good pharmacokinetic and inert pharmacological characteristics in mice and humans and is currently the most commonly used type of DREADDs artificial ligand.
Commonly used DREADDs include:
Basic Steps of Chemical Genetics
DREADDs receptor selection
Based on different experimental purposes, investigators need to select different types of DREADDs receptors that match the experimental purpose.
DREADDs receptor expression
The gene fragment of the selected DREADDs receptor is transferred into the target cells by viral vector tools, or the gene information of the DREADDs receptor is transmitted to the target cells by transgenic model animals, etc.
Administration of CNO treatment
After expression of DREADDs receptor, CNO treatment can be artificially given to target cells or animals (animals can be injected with CNO intraperitoneally or fed CNO, etc.) to achieve control of neuronal activity.
Validation of manipulation effects
Similar to optogenetic techniques, electrodes are generally used at the cellular level to record voltage changes inside and outside the neuronal cell membrane as a way to verify the effectiveness of the technique. At the macroscopic level, animal behavioral tests can be used to assess whether changes in neuronal activity have an effect on animal behavior.
At Creative Biolabs, by leveraging our expertise and state-of-the-art resources, we are committed to supporting neuroscientists and researchers around the world in unlocking the complexity of the brain's neurons. Contact us to take us on a research journey together.
Sternson S M and Roth B L. Chemogenetic tools to interrogate brain functions. Annual review of neuroscience, 2014, 37: 387-407.
Atasoy D and Sternson S M. Chemogenetic tools for causal cellular and neuronal biology. Physiological reviews, 2018, 98(1): 391-418.