LTP in cortical input could be induced by presynaptic NMDAR blockage.

<p><b>A</b>, Schematic representation of the slice preparation showing positions of stimulation (S_cortical and S_thalamic) and recording electrode (R). S_cortical and S_thalamic were positioned to activate cortical and thalamic input, respectively. EC: external capsule. LA: the lateral nucleus of amygdala. <b>B</b>, A diagram illustrating the pre-LTP protocol: low-frequency stimulation of either thalamic or cortical input at holding potential of -70 mV. Detailed pattern, 240 pluses (2-Hz frequency) consisting of paired pulse stimulation (50 ms interval) is shown above the sign. <b>C</b>, EPSC in thalamic input was potentiated to 163 ± 20% of baseline by delivering pre-LTP protocol at the arrow (n=7, paired <i>t</i> test, p<0.05 versus baseline). <b>D</b>, The same protocol failed to produce LTP in cortical input (101 ± 6% of baseline, n=8, paired <i>t</i> test, p=0.86 versus baseline). <b>E</b>, However, it succeed to induce LTP with the addition of D-AP5 (50 µM) to the external solution (161 ± 12% of baseline, n=8, paired <i>t</i> test, p<0.01 versus baseline). Inserted traces (<b>C</b>-<b>E</b>) averages of 15 EPSCs recorded before (1) and 35-40 min after induction (2, arrow). <b>F</b>, Normalized LTP showing the effect of NMDAR on LTP induction at cortico-LA synapse. Insets: averaged EPSC recorded before (1) and after first (2, left arrow) and second inductions (3, right arrow). Scale bar (<b>C</b>-<b>F</b>) 50 pA, 20 ms. <b>G</b>, Superimposed first and last NMDAR-mediated EPSCs recorded at + 30 mV blocked by intracellular dialysis either with or without MK-801(control) in the presence of CNQX (20 µM). Scale bar: 50 pA, 50 ms. <b>H</b>, Summary showing the inhibition of NMDARs-mediated EPSCs with or without MK-801(control). <b>I</b>, Under control condition (without MK-801), EPSC in cortical input remained at 93 ± 8% of baseline (n=3, paired <i>t</i> test, p=0.99 versus baseline). Even after selective postsynaptic NMDAR blockade by MK-801, potentiation was still prevented (93 ± 8% of baseline, n=6, paired <i>t</i> test, p=0.37 versus baseline). Insets: superimposition of averaged EPSCs recorded before and after induction. <b>J</b>, Potentiation was readily induced under both the selective postsynaptic NMDAR blockade and bath-applied D-AP5. Insets: averaged EPSCs recorded before (1) and after (2) the induction. <b>K</b>, Summarized histogram showing quantification of results (<b>I</b>, <b>J</b>). <b>L</b>, EPSC in cortical input also potentiated to 158 ± 9% at physiological temperature, 35-36 °C (paired <i>t</i> test, n=5, p<0.01). Insets: average of 15 EPSCs recorded before (1) and after (2) induction (arrow). Scale bar (<b>I</b>, <b>J</b>, <b>L</b>) 50 pA, 20 ms. **p<0.01.