Molecular events in neural circuit formation
Nerve cells transmit information throughout the body through specialised attachments known as synapses. During postnatal development, the brain overproduces synapses, which are later refined by neuronal activity. This is a fundamental process because it defines mature neural circuits and is critical for memory encoding. Central to the decision of either strengthening or eliminating a particular synapse is the maturation of the NMDA receptor. However, the factors that control precise developmental timing and synapse specificity of this process, and how they affect synapse stability remain poorly understood. Seeking to address this, scientists on the EU-funded NMDAR-SYNPRUN (The roles of juvenile NMDA receptors in synapse maturation and elimination and their association with cognition) project set out to investigate the mobility of the receptor within the plasma membrane and its distribution between synaptic and extrasynaptic sites. Functional NMDA receptors are heterodimers of GluN1, GluN2 and GluN3 subunits, each conferring distinct properties, and influencing receptor signalling and localisation on the neuronal surface. Research focused on the mobility of GluN3 NMDA receptors and the role of GluN3 subunits in synaptic NMDA receptor activity. Scientists observed that GluN3A expression affects the diffusion dynamics and synaptic accumulation of GluN2A NMDA receptors in immature neurons. They proposed that early after birth, high GluN3A levels keep mature GluN2A subunits away from synapses while maturation of adult neuronal networks is driven by GluN3A down-regulation. Considerable focus was also placed on deciphering the role of the GluN3A-mediated signalling pathway in determining spine density and size in neurons. Various disorders of cognition are associated with disturbances in the balance between synapse maturation and elimination. The findings of the NMDAR-SYNPRUN study have the potential for clinical application in areas such as targeted therapy for neurological conditions.
Keywords
Nerve cells, synapses, memory encoding, NMDA receptor, development, signalling, GluN3A
