GluN1

Imaging neuronal morphology and activity pattern in developing cerebral cortex layer 4

Establishment of precise neuronal connectivity in the neocortex relies on activity-dependent circuit reorganization during postnatal development. In the mouse somatosensory cortex layer 4, barrels are arranged in one-to-one correspondence to whiskers on the face. Thalamocortical axon termini are clustered in the center of each barrel. The layer 4 spiny stellate neurons are located around the barrel edge, extend their dendrites primarily toward the barrel center, and make synapses with thalamocortical axons corresponding to a single whisker. These organized circuits are established during the first postnatal week through activity-dependent refinement processes. However, activity pattern regulating the circuit formation is still elusive. Using two-photon calcium imaging in living neonatal mice, we found that layer 4 neurons within the same barrel fire synchronously in the absence of peripheral stimulation, creating a ''patchwork'' pattern of spontaneous activity corresponding to the barrel map. We also found that disruption of GluN1, an obligatory subunit of the N-methyl-D-aspartate (NMDA) receptor, in a sparse population of layer 4 neurons reduced activity correlation between GluN1 knockout neuron pairs within a barrel. Our results provide evidence for the involvement of layer 4 neuron NMDA receptors in spatial organization of the spontaneous firing activity of layer 4 neurons in the neonatal barrel cortex. In the talk I will introduce our strategy to analyze the role of NMDA receptor-dependent correlated activity in the layer 4 circuit formation.

DEVELOPMENT OF A NOVEL OPEN-CHANNEL BLOCKER FOR GLUN1/GLUN2 NMDA RECEPTORS: MECHANISM AND PHARMACOLOGY

FENS Forum 2026

GLUN1/GLUN3A EXCITATORY GLYCINE RECEPTORS CONTROL VENTRAL HIPPOCAMPAL SYNAPTIC PLASTICITY AND ANXIETY-RELATED BEHAVIORS

FENS Forum 2026

Human anti-GluN1 autoantibodies induce defective synaptic plasticity dependent on CaMKII and DAPK1 pathways as investigated by super-resolution microscopy

Pathogenic mutation GluN1-N650K in combination with GluN2A subunit changes kinetic parameters and conductance of NMDA receptors

Widespread expression and action of GluN1/GluN3A excitatory glycine receptors in the adult brain

Acute effects of human monoclonal anti-GluN1 autoantibodies on NMDA-receptor channel function

The role of disulfide bonds in GluN1 in the regulation of the early trafficking and functional properties of GluN1/GluN2 subtypes of NMDA receptors

FENS Forum 2024

The role of disulfide bonds in GluN1 in the regulation of the early trafficking and functional properties of GluN1/GluN3A subtypes of NMDA receptors

FENS Forum 2024

Human anti-GluN1 autoantibodies affect CaMKII and DAPK1 pathway dependent synaptic plasticity in primary hippocampal mouse neurons

FENS Forum 2024

Excitatory glycine GluN1/GluN3A receptors in the adult hippocampus