Figure 2.

Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during SE. (A) NMDA-mEPSC mean traces from a typical granule cell from a control (red) and a SE animal (black), demonstrating larger amplitude and area under the curve (AUC) in the latter. (B) Subcellular distribution of NMDA NR1 subunit–LI during SE. Hippocampal sections through CA3 of control (a1) and SE (b1) brains stained with antibodies against the NR1 subunit–LI (red) and against the presynaptic marker synaptophysin–LI (green), with overlaps appearing yellow. Hippocampal sections of CA3 at higher magnification are shown in a2 and b2. Note increased NR1 subunit–LI colocalization with synaptophysin–LI in pyramidal cells for SE rat (bar: 40 μm left panel; 10 μm right panel). (C) The number of colocalizations increases with NKB SE at both the soma and proximal dendrites of CA3 pyramidal cells (error bars show ± SEM). (D) Model of our hypothesis of NMDAR trafficking during the transition of single seizures to SE. After repeated seizures, in NMDA synapses, subunits are mobilized to the synaptic membrane and assemble into additional receptors. They may move initially to the perisynaptic area, then laterally to the synaptic area. As a result of this trafficking, the number of functional NMDARs per synapse increases.