Plasticity in Single Axon Glutamatergic Connection to GABAergic Interneurons Regulates Complex Events in the Human Neocortex
Fig 2
Single fiber connections to FSINs with large EPSP show group I mGluR-dependent LTD.
(A) Paired recordings from synaptically connected layer 2–3 PCs and FSINs with large amplitude EPSCs/EPSPs show LTD. The LTD is generated by the presynaptic PC firing 40 Hz bursts (5 pulses, 40 times), while the postsynaptic cell is at Em. (A1) Partial reconstruction of one recorded PC (red, axon orange)–FSIN (blue, axon light blue) pair with large EPSCs/EPSPs. Scale 50 μm. L2–3 indicates layer 2–3. Schematic shows experimental design and color-coding for the cells and traces. Confocal micrographs illustrate vgat+ and pv+ axon bouton of the FSIN filled with neurobiotin (nb, scale 2 μm). A PC spike and averaged EPSC (5 at −60 mV) in the cell pair below. Scales 1 nA and 100 pA/5 ms. (A2) Single AP-evoked EPSP amplitude (interval 10 s) in the same experiment at baseline and following the PC 40 Hz burst firing (arrow at 0 time point). The afferent single fiber burst firing induced LTD (at 20−25 min p < 0.001, paired t-test). The EPSPs (blue, average of 5 at Em –62 mV) and presynaptic cell spikes (red) at different time points and one 40 Hz burst illustrated on top. The FSIN is at Em during the recording. (A3) Mean ± standard error of the mean (s.e.m.) in five PC–FSIN pairs with large EPSP (5.85 ± 0.59 mV at baseline, showing no failures) show prominent LTD (30 s bin, baseline-normalized, n = 5 pairs, p < 0.01, Wilcoxon test). (A4) The LTD requires group I mGluRs. A PC–FSIN pair with large EPSP in the presence of group I mGluR blockers LY367385 (100 μM) and 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP, 25 μM) (applied 5 min before the bursts indicated by arrow). The EPSPs (blue, at Em −67 mV) and presynaptic cell spikes (red) shown on top. The FSIN is at Em during recording. (A5) Mean ± s.e.m. of similar PC–FSIN pairs with large EPSPs (8.42 ± 2.83 mV in baseline, showing no failures) in four experiments (30 s bin, baseline-normalized). The underlying data are shown in S2 Data. (B) EPSP analyses indicate presynaptic LTD. (B1) LTD (n = 5) is associated with an increased ratio of the EPSP amplitude SD/mean illustrated here as decreased baseline-normalized CV−2 (mean ± s.e.m. black asterisk, p < 0.05, Mann-Whitney test). Red asterisk compared with the non-LTD experiments (n = 4) (p < 0.05, Mann-Whitney test). (B2) Likewise, the EPSP amplitude PPR (1st versus 2nd EPSP) is reduced in the LTD experiments (black asterisk, p < 0.05, Mann-Whitney test), but not in the presence of group I mGluR blockers. Red asterisk indicates significance between the groups (p < 0.05, Mann-Whitney test). Baseline-normalized time window is 20–25 min after afferent bursts. The data are available in S3 Data. (B3) Sample traces from one experiment above showing the PC firing (paired-pulse 50 ms)-evoked EPSPs in the FSIN during baseline and in LTD.