Balancing Thalamic Excitation and Inhibition by Subtype-Specific NMDA Receptor Modulation

Improperly regulated N-methyl-D-aspartate (NMDA) receptors contribute to brain changes underlying numerous seizure disorders including epileptic encephalopathies, absence epilepsy, and acquired epilepsies. Because NMDA receptors are glutamate receptors essential for excitatory synaptic transmission throughout the brain, dysregulation of these receptors can lead to the hyperexcitability seen in epilepsy.

To explore the role of NMDA receptors in epilepsy and to work towards a potential therapeutic target, Dr. Swanger and her team will test how selectively modulating the subset of NMDA receptors containing the GluN2C subunit affects excitation and inhibition in the thalamus, a brain region implicated in seizure generation and propagation. GluN2C is highly expressed in the thalamus, but not other forebrain areas; therefore, this approach has the potential to circumvent a long-standing obstacle in developing epilepsy therapies by controlling the activity of neurons known to contribute to seizures without causing brain-wide glutamate receptor modulation