Study offers new insights into how ketamine works

May 21 2024Picower Institute at MIT While scientists know its target in brain cells and have observed how it affects brain-wide activity, they haven't known entirely how the two are connected. A new study by a research team spanning four Boston-area institutions uses computational modeling of previously unappreciated physiological details to fill that gap and offer new insights into how ketamine works.

"When physicians understand what's mechanistically happening when they administer a drug, they can possibly leverage that mechanism and manipulate it," said study lead author Elie Adam, a Research Scientist at MIT who will soon join the Harvard Medical School faculty and launch a lab at MGH. "They gain a sense of how to enhance the good effects of the drug and how to mitigate the bad ones.

Blocking slows the voltage build-up across the neuron's membrane that eventually leads a neuron to "spike," or send an electrochemical message to other neurons. The NMDA doorway becomes unblocked when the voltage gets high. This interdependence between voltage, spiking and blocking can equip NMDA receptors with faster activity than its slow closing speed might suggest.

But how? Key findings Importantly, through simulations, they explained several key mechanisms in the network that would produce exactly these dynamics. "The finding that an individual synaptic receptor can produce gamma oscillations and that these gamma oscillations can influence network-level gamma was unexpected," said co-corresponding author Michelle McCarthy, a research assistant professor of math at BU. "This was found only by using a detailed physiological model of the NMDA receptor. This level of physiological detail revealed a gamma time scale not usually associated with an NMDA receptor.

Source: Healthcare Press (healthcarepress.net)

Ketamine Antidepressant Computational Modeling Cortex Depression Frequency Hospital Medical School Medicine Neuron Neurons Neuroscience Pain Receptor Research

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