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Non-Conventional NMDA Receptor Signaling in Neurons and glia

Isabel Pérez Otaño

Instituto de Neurociencias de Alicante (CSIC-UMH)

07 Oct 2022 13:00

Aketxe Room, Sede building, Leioa

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NMDA receptors are glutamate-gated ion channels with central roles in brain development, synapse plasticity and memory. They assemble as heterotetrametric combinations of 3 types of subunits (GluN1, GluN2A-D, and GluN3A-B), which functional expression varies across brain regions and developmental stages to fulfill unique functions. GluN3A-containing NMDA receptor subtypes (GluN3A-NMDARs) are rarer and typically expressed in the central nervous system during temporal windows of early postnatal development that end with the emergence of precise, mature neuronal circuits and adaptive behaviors. They have non-conventional biophysical properties compared to classical NMDAR subtypes and seem to play key roles in coupling plasticity to sensory experience and in targeting non-used synapses for pruning. Precisely how and why remain poorly understood. Recent work suggests that significant GluN3A levels are retained in adult brains in multimodal and associative regions involved in cognition, social and emotional behavior, and contribute to forms of cellular plasticity in a variety of cell types including excitatory neurons, interneurons and oligodendrocytes. I will discuss current evidence for these and other emerging roles for GluN3A-NMDARs in the physiology and pathology of the central nervous system, and newly discovered mechanisms that support their function.