A recent study conducted by researchers from MIT, Boston University, Massachusetts General Hospital, and Harvard University has shed light on how ketamine, an anesthetic and antidepressant, affects brain activity. Using a computational model, the researchers simulated the drug's interaction with NMDA receptors, which are known to play a crucial role in neuronal firing patterns and consciousness.

Ketamine is widely used in medical settings for sedation, pain control, and general anesthesia, as well as for treating treatment-resistant depression. While scientists have observed its impact on brain-wide activity, the exact mechanism through which it works has remained elusive.

The team's computational model successfully replicated the real brain waves and neural spiking observed in humans and animals under the influence of ketamine. The findings suggest that ketamine blocks NMDA receptors in the brain's cortex, disrupting neural communication and leading to altered states of consciousness.

Interestingly, the model showed that ketamine can increase gamma activity, which is associated with increased brain wave power in the fast gamma frequency range. At higher doses that induce unconsciousness, gamma waves are periodically interrupted by slow frequency delta waves, which can disrupt communication across the cortex and lead to a loss of consciousness.

The study also revealed that ketamine can disinhibit network activity by shutting down certain inhibitory interneurons. This release of inhibition allows other neurons to spike vigorously, contributing to the excited brain state induced by ketamine. Additionally, the researchers found that the bursts of spiking become synchronized into gamma frequency waves due to the stimulation of inhibitory interneurons.

The computational model also suggests a possible explanation for ketamine's antidepressant effects. It proposes that increased gamma activity under ketamine could entrain activity among neurons expressing a peptide called VIP. This could lead to the release of the VIP peptide, known for its health-promoting effects, which may contribute to the antidepressant properties of ketamine. However, this connection awaits further experimental validation.

The researchers believe that their model can provide valuable insights for physicians in using ketamine more effectively. Understanding the mechanisms through which the drug acts can help optimize its therapeutic benefits while minimizing potential negative effects.

Further research and experimentation will be necessary to fully uncover the intricacies of ketamine's effects on the brain. However, this study represents a significant step forward in unraveling the mysteries behind ketamine's therapeutic properties and may pave the way for the development of more targeted treatments for depression and other neurological disorders.

The study was supported by various foundations and institutions, including The JPB Foundation, The Picower Institute for Learning and Memory, and the National Institutes of Health. The findings were published in the Proceedings of the National Academy of Sciences on May 20.