What can animal electrophysiology tell us about the human brain?
By Anastasiia Gryshyna
Throughout history, each discipline has had its moment of inspiration. For physicists, it was a falling apple that guided Newton in the understanding of gravity. For molecular biologists it was fungus that motivated Dr. Fleming in discovering penicillin. But for electrophysiologists, it was a frog.
It all started in the 18th century, when Luigi Aloisio Galvani was experimenting with frog leg muscles and saw that they twitch when an electrical shock is applied. It took many years for scientists to understand why electrocuting the leg resulted in muscle twitches. However in the 1840s, the field of electrophysiology flourished with the discovery of neuronal communication via electrical stimulation (Rubaiy, 2017). This discovery demonstrated that electrical stimulation activates motor neurons in our spinal cord, which in turn transmits electrical impulses to the brain to initiate muscle contraction.
… electrical stimulation activates motor neurons in our spinal cord, which in turn transmits electrical impulses to the brain to initiate muscle contraction.
The principle of electrophysiology is to study communication via electrical activity in tissues and organs within our body (such as muscles and brain). To better understand that communication, scientists study specialized cells called neurons that transmit information between different areas of the central nervous system and peripheral nervous system to facilitate a variety of thoughts, behaviors, and perceptions. Neurons communicate by sending electrical impulses to each other, and you can learn more about neuron communication here! These impulses contain messages which can be passed down to the next neuron (Baslow, 2009; Lovinger, 2008).
However, if the communication between neurons is disrupted, it can lead to disease, which electrophysiology helps us to understand and potentially treat. For example, electrophysiology allowed scientists to study the effects of puffer fish toxin on the human body. If you dare to touch or ingest puffer fish, you may end up paralyzed or even die! This phenomenon is observed because puffer fish contain tetrodotoxin (TTX), a neurotoxin which disrupts neuronal communication (Li et al., 2013). Using electrophysiology, scientists were able to determine the lethal dose of TTX and how to detect the toxin, which helped doctors to diagnose TTX poisoning in those who encountered this deadly animal (Sasaki et al., 2008)! Furthermore, that same toxin, in lower doses, is being investigated as a potential alternative anesthetic, which demonstrates the versatility of electrophysiology as it relates to the study of our brain and body (Li et al., 2023).
It would be very difficult to find the lethal dose of puffer fish toxin if we did not have animal models, since most people would not be willing to ingest a deadly toxin in the name of science. Animal research is an important step in understanding diseases, and the findings from animal research can be used to help scientists develop medicines. This process is better known as translational research, and electrophysiology is only one field of many that help scientists in the development of therapeutics. Today animal electrophysiology is useful in understanding a wide variety of different diseases by exploring how the nervous system behaves under various conditions and diseases. However, for the purposes of this article we will try to understand how electrophysiology helps scientists to unravel the mechanisms of neurodegeneration specifically. Since the exact cause of many neurodegenerative disorders is unknown, this serves as a significant barrier when trying to develop better and effective treatment options.
Today animal electrophysiology is useful in understanding a wide variety of different diseases by exploring how the nervous system behaves under various conditions and diseases.
One important neurodegenerative disease being explored using electrophysiology is Parkinson’s disease (PD). A major symptom of PD is movement dysfunctions, such as slow movement and gait freezing. Using electrophysiological recordings in mice, scientists have demonstrated that a specific population of neurons in the brain (called glutamatergic neurons) play an important role in movement and can be targeted using certain therapeutics (Fougère et al., 2021). Consequently, studies like this may serve efforts to alleviate some of the debilitating symptoms of Parkinson’s disease. Similarly, dysfunction of certain inhibitory neurotransmitters (molecules that can help inhibit unwanted movement) in mouse models of Parkinson’s disease has been linked to tremor during electrophysiological studies (Kralic et al., 2005). Subsequently, these inhibitory neurotransmitters have been explored as a potential therapeutic in several clinical trials of PD-associated movement dysfunctions (Di Luca et al., 2022).
Other than exploration of biological molecules (such as neurotransmitters described above) that can be used to develop medicine, electrophysiological recordings in animal models of Parkinson’s also help scientists understand how already developed medicines can be improved. Levodopa is a medication that is commonly prescribed to people with Parkinson’s disease, and although it helps to improve quality of life, it can also result in involuntary and erratic body movements. Using animal electrophysiology, scientists were able to understand why this side effect occurs and what therapeutics can be developed to prevent it (Suárez et al., 2014).
Animal electrophysiology allows scientists to understand the body-brain connection in ways that would not be possible to perform in humans. This field can be considered one of the fundamental branches of basic science– science that aims to understand underlying mechanisms of diseases. Therefore, animal electrophysiology serves as a building block in the discovery of many medicines and therapeutics. Thus, it really was a muscle twitch in a frog that moved many clinical developments forward. And if a frog can be a muse to Dr. Galvani, who knows? Maybe there is a muse right under your nose that can facilitate a great scientific discovery.
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Written by Anastasiia Gryshyna
Illustrated by Sneha Chaturvedi
Edited by Liza Chartampila and Zoë Dobler
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References
Baslow, M. H. (2009). The languages of neurons: an analysis of coding mechanisms by which neurons communicate, learn and store information. Entropy, 11(4), 782-797. https://doi.org/10.3390/e11040782
Di Luca, D. G., Reyes, N. G. D., & Fox, S. H. (2022). Newly approved and investigational drugs for motor symptom control in Parkinson’s disease. Drugs, 82(10), 1027-1053. https://doi.org/10.1007/s40265-022-01747-7
Fougère, M., van der Zouwen, C. I., Boutin, J., Neszvecsko, K., Sarret, P., & Ryczko, D. (2021). Optogenetic stimulation of glutamatergic neurons in the cuneiform nucleus controls locomotion in a mouse model of Parkinson’s disease. Proceedings of the National Academy of Sciences, 118(43), e2110934118. https://doi.org/10.1073/pnas.2110934118
Kralic, J. E., Criswell, H. E., Osterman, J. L., O’Buckley, T. K., Wilkie, M. E., Matthews, D.B., Hamre, K., Breese, G. R., Homanica, G. E., & Morrow, A. L. (2005). Genetic essential tremor in γ-aminobutyric acid A receptor α1 subunit knockout mice. The Journal of clinical investigation, 115(3), 774-779. http://dx.doi.org/10.1172/JCI23625
Lovinger, D. M. (2008). Communication networks in the brain: neurons, receptors,neurotransmitters, and alcohol. Alcohol Research & Health, 31(3), 196-214. PMID: 23584863; PMCID: PMC3860493.
Rubaiy, H. N. (2017). A short guide to electrophysiology and ion channels. Journal of Pharmacy & Pharmaceutical Sciences, 20, 48-67. https://doi.org/10.18433/J32P6R
Sasaki, K., Takayama, Y., Tahara, T., Anraku, K., Ito, Y., & Akaike, N. (2008). Quantitative analysis of toxin extracts from various tissues of wild and cultured puffer fish by an electrophysiological method. Toxicon, 51(4), 606-614. https://doi.org/10.1016/j.toxicon.2007.11.008
Suárez, L. M., Solís, O., Caramés, J. M., Taravini, I. R., Solís, J. M., Murer, M. G., & Moratalla, R. (2014). L-DOPA treatment selectively restores spine density in dopamine receptor D2–expressing projection neurons in dyskinetic mice. Biological psychiatry, 75(9), 711-722. https://doi.org/10.1016/j.biopsych.2013.05.006
Li, X., Li, Q., Song, S., Stevens, A. O., Broemmel, Z., He, Y. Wesselman, U., Yaksh, T., & Zhao, C. (2023). Emulsion‐Induced Polymersomes Taming Tetrodotoxin for Prolonged Duration Local Anesthesia. Advanced Therapeutics, 6(1), 2200199. https://doi.org/10.1002/adtp.202200199
