Differential Contributions of NMDA Receptor Subtypes to Lamina II Synaptic Responses Across Juvenile Spinal Cord Development

Abstract

NMDA receptors are heteromeric complexes crucial to the regulation of excitatory synaptic transmission, including in the spinal cord. The presence of specific subtypes of GluN2 subunits determines the kinetic properties of receptor activity. The Hildebrand lab has demonstrated that slow-decaying GluN2B and GluN2D dominate NMDAR responses at lamina I adult spinal synapses, which is unlike the fast GluN2A-dominated synapses found throughout most of the mature CNS. The functional contribution of specific GluN2 subunits is less characterized for synaptic NMDAR responses in lamina II neurons. We performed whole-cell patch clamp recordings of mEPSCs in the presence and absence of subtype-specific NMDAR pharmacological blockers. We observed a relatively equal and stable contribution of GluN2A and GluN2B throughout lamina II development, contrasting the shift in contribution from GluN2B to GluN2A commonly observed during postnatal development in the brain. We also identified a slower synaptic NMDAR component that is blocked by a GluN2D antagonist.