Fascinating New Research Unveils How Ketamine Functions as an On/Off Switch in the Brain
By: April Carson
Penn Medicine researchers have conducted a new study that reveals ketamine, which is known as an anesthetic and has been used more recently to treat depression, completely reorganizes neuron activity in the brain - almost like flipping a switch. A study revealed in Nature Neuroscience uncovered that ketamine triggered extreme alterations to the neural activity patterns in the cerebral cortex of animal models. Unexpectedly, neurons typically active were hushed while those usually dormant abruptly switched on.
This indicates that the drug changes the neurons in the brain so they react differently to stimuli and affect long-term memory formation. Further research is needed to explore how ketamine works exactly, as well as its potential clinical applications.
This newfound discovery of how ketamine amplifies activity in essential brain regions associated with depression could revolutionize our understanding of the drug's therapeutic effects, and also open new doors for advanced neuropsychiatric research. Over the years, psychiatrists have struggled to understand why some patients respond positively to ketamine while others do not. With this knowledge, we could soon develop targeted treatments for depression and other mental health disorders that are more effective than current methods.
In a groundbreaking new study, Joseph Cichon MD, Ph.D., an assistant professor of Anesthesiology and Critical Care and Neuroscience at the Perelman School of Medicine at the University of Pennsylvania revealed two distinct populations of cortical neurons: one that is active during normal awake brain states, and another engaged when under ketamine-induced conditions.
It's conceivable that this novel network brought about by ketamine allows dreams, hypnotism, or some form of unconscious state to exist. If proven correct, this could hint at the fact that it is where ketamine’s therapeutic actions occur. To test out his hypothesis, Cichon and team conducted experiments using optogenetics -- a technique used to genetically engineer neurons to control their activity with light.
Anesthesiologists have been using the drug ketamine since its synthesis in the 1960s to safely induce unconsciousness for surgeries. Ketamine is an effective drug due to its reliable physiological effects and excellent safety profile, making it a preferred choice among anesthetists worldwide. Ketamine stands out from other anesthetics due to its ability to keep some brain activity going across the cortex. This is thought to be what enables ketamine's capacity for treating depression in key cortical regions connected with this disorder. Nonetheless, it remains unclear how exactly ketamine produces these therapeutic results.
Recent research conducted by scientists at the University of Auckland in New Zealand has uncovered new insights into how ketamine works. Researchers investigated the drug's effect on cortical neurons in mice and discovered that ketamine acts as a kind of "on/off switch" for certain neuron populations in the brain.
In their groundbreaking research, the scientists evaluated how ketamine affected mouse behavior in comparison to mice who were given a placebo saline. By observing behaviors before and after administering the drug, they sought to better understand its potential effects. The effects of ketamine were quickly observed in those receiving the drug, as they showed a reduction in locomotion and sensorial responses - commonly known as "dissociation" - within moments after being injected.
Co-lead and co-senior author Alex Proekt, MD, Ph.D., an associate professor of Anesthesiology and Critical Care at Penn states that the goal was to uncover precisely which regions in the brain circuit ketamine affects when administered so further research can be conducted on it leading towards more beneficial applications for therapeutic purposes.
Through extensive research and experiments, the team identified a key mechanism that occurs in the brain when ketamine is introduced. Using optogenetics - a technique used to activate or inhibit neurons using light - they discovered that ketamine acts as an “on/off switch” for circuits involved in consciousness.
With two-photon microscopy, scientists were able to observe cortical brain tissue before and after ketamine administration. Astonishingly, they noticed that the drug activated dormant cells while deactivating those which had been active before treatment. By tracking individual neurons and their behavior, this exciting discovery was made possible.
The team concluded that, by acting as an on/off switch in the brain, ketamine might be able to help treat disorders such as depression and anxiety.
By studying ketamine’s ability to block NMDA receptors and HCN channels located in synaptic junctions between neurons, the researchers discovered that they could replicate its effects without needing to use medications. By simply inhibiting these particular receptors and ion channels within the cortex, similar neuronal activity was observed. The scientists discovered that ketamine weakens several sets of inhibitory cortical neurons, which often tamp down other neurons. As a result, normally dormant neurons were activated when the drug was present.
According to the research, a decrease in inhibition was essential for excitatory neurons - which act like communication pathways and are the main focus of antidepressant medications frequently prescribed - to make an activity switch. To fully understand ketamine's remarkable capability to rapidly reduce depressive symptoms, further research needs to be done to determine if its effects on excitatory and inhibitory neurons are driving its success.
What has been established by this latest study is that ketamine works by turning certain neurons in the brain on and off. This knowledge could be applied to develop new treatments for depression that are more effective, faster-acting, and longer-lasting than existing medications.
Max Kelz, MD, Ph.D., a distinguished professor of Anesthesiology and vice chair of research in Anesthesiology and Critical Care, comments that while their study focuses on basic neuroscience findings, it has led to the realization of the potential uses for ketamine as an effective antidepressant with fast-acting results. This requires further investigation, but the neural alteration we identified may also be responsible for dissociative and hallucinatory experiences in some mental health conditions.
The exciting findings from the research may inform further clinical trials, evaluate potential risks, and assess how ketamine might be used to treat other mental health conditions. The team is now working on further research to understand the mechanisms that control these neurons and how they could be manipulated for therapeutic uses.
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April Carson is the daughter of Billy Carson. She received her bachelor's degree in Social Sciences from Jacksonville University, where she was also on the Women's Basketball team. She now has a successful clothing company that specializes in organic baby clothes and other items. Take a look at their most popular fall fashions on bossbabymav.com
To read more of April's blogs, check out her website! She publishes new blogs on a daily basis, including the most helpful mommy advice and baby care tips! Follow on IG @bossbabymav
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