Plasticity in Single Axon Glutamatergic Connection to GABAergic Interneurons Regulates Complex Events in the Human Neocortex
Fig 3
LTD fails in weak single-fiber PC-FSIN connections, but is generated by coactivity of multiple glutamatergic fibers.
(A) LTD fails in PC–FSIN pairs with small EPSP. (A1) Schematic shows experimental design. A presynaptic PC spike (red) with postsynaptic EPSCs (blue, average of 5 at −60 mV) in one recording and confocal micrographs of the FSIN axon (nb, neurobiotin) with pv+ boutons (scale 5 μm, arrows point colabeling in merged image). (A2) One PC–FSIN pair with the EPSPs in baseline and after the afferent cell 40 Hz bursts (arrow). Averaged EPSPs (5) at Em −72 mV on top at different time points and a 40 Hz burst. Postsynaptic cell is at Em (current clamp) during the recording and the bursts. (A3) Mean ± s.e.m. (30 s bin, baseline-normalized) of similar experiment in five PC–FSIN pairs with small amplitude EPSPs (1.89 ± 0.43 mV in baseline with failures). (A4) Failure of the LTD in weak PC–FSIN connections is not due to insufficient postsynaptic depolarization. Plot shows EPSP in one PC–FSIN pair before and following the presynaptic bursts, now paired with FSIN depolarization beyond the firing threshold (see Methods). Averages of EPSPs (5 at Em −66 mV) and a 40 Hz burst with simultaneous depolarization (30 mV, 250 ms) in voltage clamp shown on top. (A5) Mean ± s.e.m. of five similar experiments with small EPSP (1.44 ± 0.22 mV in baseline with failures) PC–FSIN pairs (baseline-normalized, 30 s bin). The underlying data are shown in S4 Data. (B) Connections between PCs exhibit small amplitude EPSPs with no long-term plasticity when PC1 bursts, while PC2 is at resting membrane potential. (B1) EPSP amplitude in one experiment before and after the 40 Hz presynaptic cell bursts (arrow, postsynaptic cell at Em −78 mV). Averaged EPSPs (five at Em) shown on top with a 40 Hz burst, and a schematic showing the experimental design. (B2) Mean ± s.e.m. of baseline-normalized EPSPs (1.40 ± 0.30 mV in baseline with failures) in four PC–PC pairs as in B1 (30 s bin) (S4 Data). (C) Activation of multiple afferent pathways to FSINs using extracellular stimulation reveals group I mGluR-dependent LTD in weak PC–FSIN synapses (S5 Data). (C1) One experiment with monosynaptic EPSC in FSIN (voltage clamped at −60 mV) at baseline and following the 40 Hz bursts applied to the stimulation pathway (arrow at 0 time point). Inset traces (averages of 5) show evoked EPSCs in baseline and in LTD. The monosynaptic component is indicated by dotted vertical line. Schematic shows experimental design. (C2) Mean ± s.e.m. of seven baseline-normalized experiments as in C1 showing the LTD in control conditions (open symbols, p < 0.001, paired t-test) and blockade of the LTD in experiments with LY367385 (100 μM) and MPEP (25 μM) (solid symbols, n = 7, paired t-test). (C3) Generation of group I mGluR-dependent LTD by 40 Hz stimulation is conserved in mammalian neocortex occurring also in rat FSINs. Multiple fiber extracellular stimulation with LTD in rat L2–3 somatosensory cortex FSINs. Open symbols show experiments in control conditions (n = 5, p < 0.01) and solid symbols in the presence of LY367385 (100 μM) and MPEP (25 μM) (n = 5) (Wilcoxon test). Blockers for glutamate N-methyl-D-aspartatereceptors (NMDARs) (DL-2-Amino-5-phosphonopentanoic acid; DL-APV, 100 μM) and GABAARs (PiTX, 100 μM) were present in C1–C3. (C4-C5) Likewise, LTD of the EPSCs in both species is associated with an increased amplitude SD versus the mean. Data shows decreased CV−2 (baseline-normalized at 20 min after 40 Hz) in LTD in control conditions, but not when LTD is blocked in the presence of group I mGluR blockers (p < 0.05 between groups, Mann-Whitney test).