Figure 1

NMDAR-mediated responses are not depressed by low-frequency stimulation (LFS) at silent synapses in synaptically connected pairs of CA3 pyramidal neurons. A. Silent synaptic connections between pairs of CA3 pyramidal neurons [10]showed no synaptic responses when the postsynaptic cell was held at a negative potential (-65 mV). Depolarization of the postsynaptic cell to +40 mV revealed the NMDAR-mediated EPSC of these silent synapses. LFS did not cause any change in this NMDAR-only synaptic transmission (n = 7 pairs). Inset: Each inset shows consecutive postsynaptic traces overlaid, with one example presynaptic action potential. (1) 50 consecutive postsynaptic responses collected from the start of the paired recording, showing no AMPAR-mediated responses at -65 mV. (2). At +40 mV, NMDAR mediated responses are evident. (3) After performing LFS, NMDAR mediated responses are shown at +40 mV. For both (2) and (3), 10 consecutive traces are shown, before LFS (2), and ten minutes after LFS (3). B. The same LFS protocol applied to active synapses does depress the NMDAR-mediated EPSC (n = 6 pairs). After confirmation that a synaptic connection displayed AMPAR-mediated responses, NMDAR EPSCs were isolated by application of 10 μM NBQX. Inset shows ten consecutive postsynaptic traces collected at -65 mV before (1) and after (2) NBQX and +40 mV in NBQX, before (3) and 10 minutes after (4) LFS. An exemplar presynaptic action potential is shown in each case. Closed symbols: LFS-treated, open symbols, no LFS applied.