Fig. 7
Differential impact of ambient glutamate on synaptic NMDAR responses in excitatory and inhibitory neurons. a Ambient glutamate activation of synaptic NMDARs was assayed by measuring the use-dependent blockade by MK-801 in the absence of synaptic stimulation (see text). Synaptic NMDAR EPSCs were reduced by MK-801 application in the absence of synaptic stimulation in inhibitory neurons but not excitatory neurons and this reduction was ameliorated in inhibitory neurons from Cef-treated mice. Sample traces of NMDAR EPSCs before and after MK-801 application in an inhibitory neuron (left), an excitatory neuron (middle), or an inhibitory neuron from a Cef-treated mouse (right). Scale bars, 10 pA/100 ms (left); 30 pA/100 ms (middle); 10 pA/100 ms (right). No significant change in NMDAR EPSCs area was observed after MK-801 in excitatory neurons (N = 6), while a significant reduction was observed in inhibitory neurons (N = 9; ***P < 0.001, 113.1 ± 8.25% (Ext), 73.67 ± 4.97% (Int), unpaired t test, compared to excitatory neurons). Inhibitory neurons in Cef-treated mice showed a significantly reduced effect of MK-801 application (N = 13; 73.67 ± 4.97% (Int), 93.44 ± 6.52% (Ext). *P < 0.05, unpaired t test, compared to inhibitory neurons without Cef injection). b A model depicting the differential resting glutamate levels in the synaptic cleft in excitatory (left) and inhibitory (right) neurons, likely caused by difference in the density/activity of glutamate transporters (such as GLT-1s). Error bars represent SEM. ns not significant
