Optogenetics, and more recently chemogenetics, are bringing to light answers that address the shortcomings of pharmaceutical or electrode use in brain research. They both allow for the precise control of neurons, and have facilitated major advances in neuroscience and neuroendocrinology research.
Non-invasive vs temporally precise
Optogenetics and chemogenetics both have pros and cons. Optogenetics is extremely temporally precise, for example, but to get light into the brain, which this technique requires, implants and wires are needed.
Chemogenetics uses the DREADD technology (Designer Receptors Exclusively Activated by Designer Drugs), sensitizing neurons for activation by a specific drug-like molecule. These actuators can be put in the animal’s drinking water, making this a non-invasive method, but it is not as temporally precise as some experiments require. Additionally, repeated activation means repeated administrations, which is not that efficient.
Last year a new method found its way into neuroscience related journals: the use of electromagnetic control, or Magnetogenetics, as some call it. As you may have guessed, this involves activating cells using magnetic fields. With magnetogenetics, researchers have a non-invasive method that seems to have the best of both: this technique is non-invasive, yet temporally precise. It is also effective in deep brain tissue, works in several areas simultaneously, suitable for long-term studies, and relatively safe. This method even seems to show promise in some clinical applications.
Case #1: Creating the “dream tool”
Similarly to optogenetics and chemogenetics, neuronal cells are sensitized for activation; the activator in this case is instead a magnet. To accomplish this, researchers fused the nonselective cation channel TRPV4 to the paramagnetic protein ferritin, creating the tool “Magneto” which can be delivered through a single viral vector into the brain region of interest.
In March 2016 Michael Wheeler and his colleagues at the University of Virginia reported their findings of using electromagnetic control in Nature Neuroscience. They demonstrated the effectiveness of Magnetogenetics in vitro and in vivo in both zebrafish and mice. Ali Deniz Güler (leading biology professor) says they might have discovered a ‘dream tool’ in controlling neural circuits.
In further experiments, they developed Magneto2.0 to control DR1 (dopamine receptor 1) while mice were exposed to a magnetized chamber. Researchers were able to record an increase in firing rate from these neurons, confirming the possibility of controlling deep brain tissue. Then, in a real-time place preference test, mice preferred the magnetized arm, as the magnets activated the dopamine neurons sufficiently to serve as a reward for the mice. Behavioral measurements were taken automatically with EthoVision XT video tracking.
Read more about this study in this blog post.
Case #2: Controlling feeding behavior
For many reasons, much research is carried out examining feeding behavior, weight, and blood glucose levels. The ventral medial nucleus of the hypothalamus has been the focus of many of these studies, as it is known to regulate feeding behavior. To understand the neurological pathways underlying homeostasis disturbances, blood glucose levels, feeding behavior disorders, etc., and to explore treatment options, tools like electromagnetic control or magnetogenetics show great promise.
Also in March 2016, Sarah Stanley and her colleagues from the Rockefeller University in New York published their finding using electromagnetics to study how the brain controls glucose homeostasis and feeding in mice. In this case, TRPV1 was fused to ferritin. Using an electromagnetic field, and targeting the ventromedial hypothalamus, researchers were able to remotely turn feeding behavior on and off in mice.
Complete behavioral and equipment control
The creation of new tools such as Magneto furthers scientific inquiry by leaps and bounds. EthoVision XT video tracking software can do the same for behavioral assessments. With EthoVision XT researchers are able to carry out complete behavioral experiments; full system integration allows real-time control of hardware based on timing and/or animal behavior. Many behavioral paradigms of interest are automatically measured and assessed, to easily examine behavioral impacts of innovative new neuroscience tools. For more information, click here.
- Funderburk, S.C.; Krashes, M.J. (2016). Electromagnetic control of neural activity – prospective physics for physicians. Nature Reviews Neuroendocrinology, 12, 316-317.
- Wheeler, M.A.; Smith, C.J.; Ottolini, M.; Barker, B.S.; Purohit, A.M.; Grippo, R.M.; Gaykema, R.P.; Spano, A.J.; Beenhakker, M.P.; Kucenas, S.; Patel, M.K.; Deppmann, C.D.; Güler, A.D. (2016). Genetically targeted magnetic control of the nervous system. Nature Neuroscience, 19, 756-761.
Read more about this study in this blog post.
- Stanley, S.A.; Kelly, L.; Latcha, K.N.; Schmidt, S.F.; Yu, X.; Nectow, A.R.; Sauer, J.; Dyke, J.P.; Dordick, J.S.; Friedman, J.M. (2016). Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature, 531, 647-666.