NMDA receptors are saddled with an unwieldy name, but they are some of the most important* signaling molecules in the brain, both for learning and memory and in neurological and psychiatric diseases.
Kasper Hansen, a postdoc from Stephen Traynelis’ lab who is establishing his own at the University of Montana, is lead author on a recent paper in Neuron, which could spur research on NMDA receptors’ pharmacological properties.
The NMDA receptors in the brain are actually mix-and-match assemblies of four subunits, and most of the time in the brain, three different proteins come together to make one receptor, the authors explain. In the laboratory, it has been easier to study simpler, more homogenous, but also more artificial constructs. Hansen and his colleagues developed a way to build replicas of the more complicated NMDA receptors found in the brain and probe their distinct responses to drugs.
*Want back-up for that sweeping statement? Check out the connections between NMDA receptors and complex diseases such as autism, schizophrenia and Parkinson’s. The antidepressant effects of the NMDA receptor antagonist ketamine has been a recent bright spot in the study of depression. To be sure, NMDA receptor antagonists like ketamine have dissociative/hallucinatory effects, which get in the way of their utility vs excitotoxicity, a source of damage in stroke/brain injury. Developing more selective approaches could unlock the potential of drugs that act on NMDA receptors.