Increased NMDA NR2B receptor-mediated postsynaptic currents in adult ACC neurons is shown after inflammation. A, Confocal image of a pyramidal neuron in an adult ACC slice loaded with Lucifer yellow (top left). The arrow indicates the location of the neuron in the ACC slice (bottom left). Scale bar, 20 μm. When injected with current steps from -100 to 100 pA in 400 ms (bottom right), the neuron shown at the left fired repetitive action potentials with frequency adaptation (top right). A minority of neurons recorded (n = 4) showed the fast-spike properties (middle right). B, Current-voltage plot of the NMDA receptor EPSCs. The currents exhibited strong outward rectification and the reversal potential of the linear part was 4.4 ± 2.0 mV (n = 6 neurons/5 mice). Inset, NMDA receptor-mediated EPSCs recorded at holding potentials from -65 to 50 mV. Each trace represents the average of five consecutive recordings. C, A selective NR2B antagonist, Ro 25-6981, partially inhibited NMDA receptor-mediated EPSCs. The time course of changes in EPSC amplitude before and during the application of Ro 25-6981 (0.3 and 3 μM) and AP-5 (50 μM) in ACC neurons from both saline (control, Δ) and CFA-injected () mice is shown. Traces show the currents at different time points during application of drugs. Ro 25-6981 produced its maximal effect at 3 min after bath application, and a higher dose of Ro 25-6981 (3 μM) had no additional effects. The remaining currents can be totally blocked by AP-5 (50 μM). D, Summary data of the effects Ro 25-6981 (0.3 and 3 μM) in ACC neurons of control (saline-injected) and CFA-injected mice. Ro 25-6981 produced significantly greater inhibitory effects on NMDA receptor-mediated EPSCs in ACC neurons in CFA-injected mice (n = 9 neurons/8 mice) than those in control adult mice (n = 8 neurons/7 mice). AP-5 (50 μM) completely blocked the currents, confirming the currents are mediated NMDA receptors (n = 5 slices/5 mice). The double asterisks indicate significant difference from control, and the double daggers indicate significant difference from control NMDA receptor-mediated EPSCs. Error bars represent SEM (from Reference 24).