Inadequate synaptic activation of NMDA receptors in the Ts65Dn DG is normalized by removing extracellular magnesium or depolarization. A, Representative field responses evoked by a three-stimulus (arrowheads; S1, S2, and S3), 100 Hz train in the 2N and Ts65Dn DG (thin and thick lines, respectively). 1, fEPSPs recorded in modified ACSF before application of APV. Note after the second and the third stimuli the difference in the late phases of the responses. 2, The AMPA receptor-dependent component of fEPSP recorded in an APV-containing solution. 3, The NMDA receptor-dependent component of the responses calculated as the difference in the responses recorded before and during application of APV (i.e., “1” minus “2”). B, Averaged ratios of the NMDA-AMPA responses evoked by each of the three stimuli. The ratio was significantly smaller in the Ts65Dn DG for the second and the third stimuli. *p < 0.03. C, fEPSPs evoked by three-stimuli trains in magnesium-free modified ACSF. Total fEPSPs recorded before application of APV (1), and the AMPA receptor-mediated component of fEPSPs recorded after suppression of the NMDA receptors with APV (2), were indistinguishable in the 2N and Ts65Dn DG. Consequently, the NMDA receptor-mediated component of fEPSPs, taken as “1” minus “2,” were also indistinguishable (3). D, Averaged ratios of the amplitudes of NMDA-AMPA receptor-mediated components of fEPSP in magnesium-free ACSF. There was no difference between the 2N and Ts65Dn DG. E, Whole-cell currents recorded in the DG of slices from 2N and Ts65Dn mice at holding potentials of -80 and +40 mV. The responses at -80 mV reflect activation of AMPA receptors. The responses at +40 mV reflect activation of NMDA receptors, because at this holding potential, AMPA receptors were blocked by application of NBQX. F, Ratios of the amplitudes of the whole-cell currents recorded at +40 and -80 mV. The NMDA receptor-dependent responses were similar in the 2N and Ts65Dn DG. Open bar, 2N; filled bar, Ts65Dn. The error bars in B, D, and F represent SEM.