Reversible Control of Native GluN2B-Containing NMDA Receptors with Visible Light.

NMDA receptors (NMDARs) are glutamate-gated ion channels playing a central role in synaptic transmission and plasticity. NMDAR dysregulation is linked to various neuropsychiatric disorders. This is particularly true for GluN2B-containing NMDARs (GluN2B-NMDARs), which have major pro-cognitive, but also pro-excitotoxic roles, although their exact involvement in these processes remains debated.

Lack of evidence for direct ligand-gated ion channel activity of GluD receptors.

Delta receptors (GluD1 and GluD2), members of the large ionotropic glutamate receptor (iGluR) family, play a central role in numerous neurodevelopmental and psychiatric disorders. The amino-terminal domain (ATD) of GluD orchestrates synapse formation and maturation processes through its interaction with the Cbln family of synaptic organizers and neurexin (Nrxn). The transsynaptic triad of Nrxn-Cbln-GluD also serves as a potent regulator of synaptic plasticity, at both excitatory and inhibitory synapses.

GluD1 binds GABA and controls inhibitory plasticity.

Fast synaptic neurotransmission in the vertebrate central nervous system relies primarily on ionotropic glutamate receptors (iGluRs), which drive neuronal excitation, and type A γ-aminobutyric acid receptors (GABARs), which are responsible for neuronal inhibition. However, the GluD1 receptor, an iGluR family member, is present at both excitatory and inhibitory synapses. Whether and how GluD1 activation may affect inhibitory neurotransmission is unknown.

Mechanisms of NMDA receptor regulation.

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels widely expressed in the central nervous system that play key role in brain development and plasticity. On the downside, NMDAR dysfunction, be it hyperactivity or hypofunction, is harmful to neuronal function and has emerged as a common theme in various neuropsychiatric disorders including autism spectrum disorders, epilepsy, intellectual disability, and schizophrenia. Not surprisingly, NMDAR signaling is under a complex set of regulatory mechanisms that maintain NMDAR-mediated transmission in check.

Positive allosteric modulation of NMDA receptors: mechanisms, physiological impact and therapeutic potential.

NMDA receptors (NMDARs) are glutamate-gated ion channels that play key roles in synaptic transmission and plasticity. Both hyper- and hypo-activation of NMDARs are deleterious to neuronal function. In particular, NMDAR hypofunction is involved in a wide range of neurological and psychiatric conditions like schizophrenia, intellectual disability, age-dependent cognitive decline, or Alzheimer's disease.