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Chemogenetics refers to the use of small molecule ligands that selectively target genetically-modified receptors (DREADDs) or chimeric ion channels (PSAMs) to modulate and control neuronal activity.
Major advances in neuroscience methods have allowed researchers to selectively manipulate neural systems in awake animals, with two key techniques emerging; optogenetics and chemogenetics. Both these approaches enable the exploration of neural circuitry underlying complex behaviors in health and disease.
Chemogenetic experiments require the introduction of genetically engineered receptors or ion channels into specific brain areas, via viral vector expression systems. Ligands, that are inert except for their specific action at those receptors/ion channels, are then administered. Binding of the ligand to its target initiates changes in downstream intracellular signaling pathways or opening of an ion channel pore, enabling controlled activation or inhibition of neuronal activity, depending on the specific receptor/ion channel and ligand used. Similarly, optogenetics allows the modulation of neuronal activity via expression of light-sensitive ion channels. However, activation or inhibition of neuronal activity is initiated by implanted fibre optics, rather than small molecules. The key features of optogenetics and chemogenetics are summarized in Table 1.
|Method of intervention||Inert, small molecule ligands selective for genetically engineered receptors/ion channels||Light-sensitive ion channels activated by implanted fibre optics|
|Is the intervention 'physiological'?||Yes - uses conserved, intracellular signaling pathways, or changes ion channel conductance, to alter neuronal activity||No - patterns of excitation/inhibition are artificially synchronized by light stimulation pattern|
|Is the intervention inert?||Yes - receptors/ion channels lack pharmacological activity without ligands and ligands are pharmacologically inert without specific engineered receptors/ion channels||No - the fibre optic light source can create heat and bacterial light-sensitive channels used can be antigenic|
|Is this method invasive in vivo?||Minimally to no - ligands can be given by intracerebral infusion, intraperitoneal injection or in drinking water, dependent on specific ligand||Yes - inherently invasive due to implantation of fibre optics|
|Is specialized equipment required?||No||Yes - requires implantable fibre optics as light source|
Tocris offers the following scientific literature for Chemogenetics to showcase our products. We invite you to request* or download your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
Produced by Tocris, the chemogenetics research bulletin provides an introduction to chemogenetic methods to manipulate neuronal activity. It outlines the development of RASSLs, DREADDs and PSAMs, and the use of chemogenetic compounds. DREADD ligands and PSEMs available from Tocris are highlighted.
Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia, affecting approximately 47 million people worldwide. Updated in 2015, this poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease, as well as classic AD drug targets.
Major depressive disorder is characterized by depressed mood and a loss of interest and/or pleasure. Updated in 2015 this poster highlights presynaptic and postsynaptic targets for the potential treatment of major depressive disorder, as well as outlining the pharmacology of currently approved antidepressant drugs.
Recognition memory enables us to make judgements about whether or not we have encountered a particular stimulus before. This poster outlines the cellular mechanisms underlying recognition memory and its links to long-term depression, as well as the use of pharmacological intervention to assess the role of neurotransmitters in recognition memory.
Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.