Article Figures & Data
Figures
- Fig. 1.
The soluble guanylase inhibitor ODQ prevents the induction of LTD but not of LTP. A, In a control set of slices, LFS (900 stimuli, 1 Hz) induced LTD of field EPSPs (○);n = 6. In a second set of experimental slices, ODQ (10 μm) perfused for 1 hr before LFS inhibited the induction of LTD of field EPSPs (•); n = 7.a–d show original traces of field EPSPs in control baseline recording (a, b) after induction of LTD in control slices (d) and after block of LTD induction in the presence of ODQ. B, In a control set of slices, HFS consisting of eight trains of eight stimuli at 200 Hz induced LTP of field EPSPs (○). In a second set of experimental slices, ODQ perfused for 1 hr before HFS did not inhibit the induction of LTP of field EPSPs (•).
- Fig. 2.
The PKG inhibitor KT5823 (10 μm) inhibits the induction of LTD but not of LTP. A, In a control set of slices, LFS induced LTD of field EPSPs (○);n = 7. In a second set of experimental slices, KT5823 prevented the induction of LTD of field EPSPs (•);n = 8. B, In a control set of slices, LFS consisting of 60 stimuli at 1 Hz applied at −40 mV induced LTD of EPSCs recorded under whole-cell patch-clamp conditions (○);n = 5. In a second set of experimental slices, LTD of EPSCs was inhibited in cells filled with KT5823 by diffusion from the patch pipette (•); n = 5. C, D, In control slices, HFS consisting of one train of eight stimuli at 200 Hz (C) or eight trains of eight stimuli at 200 Hz (D) induced LTP (○);n = 5. In experimental slices, LTP of EPSCs was not inhibited in cells filled with KT5823 by diffusion from the patch pipette when LTP was induced by one or eight trains of HFS (C, D) (•); n = 5. The original traces inC show paired-pulse recordings of EPSCs in control baseline recordings (a, b) and after induction of LTP (c, d). E, The graph shows that LTP of field EPSPs induced by HFS (8 trains of 8 stimuli at 200 Hz) is not blocked by extracellular bath application of KT5823, with the amplitude of LTP induced in control (○) not significantly different from that in KT5823 (•).
- Fig. 3.
The cGMP phosphodiesterase inhibitor cGMP induces LTD. A, The top graph shows that the perfusion of zaprinast (20 μm for 20 min) resulted in the induction of LTD of the field EPSP; n = 10. Thebottom graph shows that the initial depression lasting ∼30 min was accompanied by a decrease in paired-pulse depression, indicating a presynaptic site of action. However, the remaining LTD was not accompanied by a change in paired-pulse depression. The originaltraces above the top graph show paired pulse-recordings of EPSPs in control baseline recordings (a), 10 min after washout of zaprinast (b) and 50 min after washout of zaprinast (c). The original traces below thebottom graph are the superimposed traces ofa and the normalized first EPSP of b, showing the early change in paired-pulse depression during the zaprinast perfusion. a and c area and the normalized first EPSP of c, showing the lack of change of paired pulse depression during LTD.B, Occlusion experiment showing that after induction of LTD by zaprinast, LFS did not induce further significant LTD;n = 5. The original traces are paired-pulse recordings of field EPSPs in control baseline recordings (a), 40 min after application of zaprinast (b), and 40 min after LFS (c). C, Occlusion experiment showing that after induction of LTD by LFS, zaprinast did not induce further significant LTD; n = 5. The original traces are paired-pulse recordings of field EPSPs in control baseline recordings (a), 15 min after LFS (b) and 40 min after application of zaprinast (c).
- Fig. 4.
Zaprinast-induced LTD is blocked by the inhibitors of soluble guanylyl cyclase ODQ and PKG inhibitor KT5823.A, Perfusion of the soluble guanylyl cyclase inhibitor ODQ (10 μm) inhibited the LTD of field EPSPs induced by perfusion of zaprinast (20 μm); n = 5. B, Perfusion of the PKG inhibitor KT5823 (10 μm) inhibited the LTD induced by perfusion of zaprinast (20 μm); n = 7. C, In a set of control experiments, zaprinast (20 μm) induced LTD of EPSCs (○). In the presence of postsynaptic KT5823 (10 μm in the patch pipette), zaprinast-induced LTD was inhibited (•); n = 5. D, An experiment in which the presence of KT5823 in the patch pipette inhibited the zaprinast-induced LTD of EPSCs but did not inhibit the zaprinast-induced LTD of the field EPSP. The original traces show paired-pulse recordings of field EPSPs in control baseline recordings (a) and after perfusion of zaprinast (c), which induced LTD, and also of EPSCs in control baseline recordings and in the postsynaptic presence of KT5823 (d), which blocked the induction of LTD.
- Fig. 5.
The induction of LTD by zaprinast (20 μm) requires test stimulation and activation of mGluRs, but not NMDAR. A, Cessation of test stimulation during perfusion of zaprinast significantly reduced the induction of LTD by zaprinast, although not of a short-term depression;n = 5. The original traces show recordings of EPSPs in control baseline recording (a) and after the induction of LTD by zaprinast (b).B, The mGluR antagonist MCPG (500 μm) significantly reduced the induction of LTD by zaprinast;n = 5. The original traces show recordings of EPSPs in control baseline recordings (a) and after the induction of LTD by zaprinast (b).C, The NMDAR antagonist AP5 did not significantly prevent LTD induction by zaprinast; n = 5. The original traces show field EPSPs in the control baseline recording (a) and after the induction of LTD by zaprinast (b).
