Bidirectional plasticity of excitatory postsynaptic potential (EPSP)-spike coupling in CA1 hippocampal pyramidal neurons

Abstract

Integration of synaptic excitation to generate an action potential (excitatory postsynaptic potential-spike coupling or E-S coupling) determines the neuronal output. Bidirectional synaptic plasticity is well established in the hippocampus, but whether active synaptic integration can display potentiation and depression remains unclear. We show here that synaptic depression is associated with an N-methyl-d-aspartate receptor-dependent and long-lasting depression of E-S coupling. E-S depression is input-specific and is expressed in the presence of gamma-aminobutyric acid type A and B receptor antagonists. In single neurons, E-S depression is observed without modification of postsynaptic passive properties. We conclude that a decrease in intrinsic excitability underlies E-S depression and is synergic with glutamatergic long-term depression.

Fig 1.

Reversal of E-S P. (A) Time course of the normalized EPSP slope after HFS (100 Hz) and LFS (1 Hz) in a representative slice. (Inset) Recording configuration. Dashed areas correspond to the test of E-S coupling. The stimulus intensity was restored to its initial value for tetani and EPSP-slope measurements. (B) Associated changes in E-S coupling. Blue, red, and green curves, E-S coupling before, after HFS tetanus and after LFS, respectively. After HFS, a given EPSP slope evoked a larger PS (superimposed blue and red traces). After LFS a given EPSP slope evoked a smaller PS (superimposed red and green traces). (C) Pooled data of the effect of HFS on the EPSP slope (○) and PS amplitude (•). (D) Normalized PS amplitude after induction of potentiation (red) and depotentiation (green). (E) Pooled data of the effect of LFS on EPSP slope (○) and PS amplitude (•). (F) Summary of E-S changes after HFS and LFS (P < 0.001 and P < 0.002). E-S coupling remained unchanged if the stimulus frequency was 0.3 Hz (blue line, P > 0.1).

Fig 2.

Synergic expression of synaptic and E-S plasticity. (A and B) Changes in EPSP slope and E-S coupling as a function of the tetanus frequency in naive (A) and potentiated (B) slices. (C) Plot of E-S plasticity versus synaptic plasticity in all slices.

Fig 3.

E-S P and E-S D in the presence of PTX. (A) Time-course of the synaptic potentiation and depotentiation in a representative slice. (B) Associated changes in the E-S coupling in this slice. (C and D) Pooled data for E-S P (C) and E-S depotentiation (D). (Insets) Representative potentials showing E-S P (superimposed blue and red traces) and E-S depotentiation (superimposed red and green traces). (E) E-S plasticity as a function of synaptic plasticity in potentiated and naive slices recorded in the presence of PTX. (F) Time course of E-S P (red) and E-S D (green) induced by 100 and 3 Hz tetani.

Fig 4.

E-S P and E-S D in single CA1 pyramidal cells. All experiments were performed in the presence of PTX. (A) Time course of LTP induced by HFS (○) and input resistance (•). (B) Firing probability as a function of EPSP slope before (blue) and after (red) LTP induction in one of these neurons (see superimposed traces). (C) Time course of LTD induced by LFS (○) and input resistance (•). (D) Firing probability as a function of the EPSP slope before (blue) and after (green) LTD induction in one of these neurons. The firing probability for a given EPSP slope decreased after LFS (see superimposed traces).

Fig 5.

E-S plasticity is input-specific. (A) EPSP slope and PS amplitude versus time in the tetanized (○, •, TET) and the control pathway (gray triangle, CON). (B) Pooled changes in E-S coupling for each pathway. (C–E) Assay of E-S coupling with constant stimulus strength in the presence of PTX. (C) Time course of EPSP changes in a slice. Kynurenate (kyn, 400 μM) was applied before and after each tetanus. (D) E-S P and E-S depotentiation in the experiment illustrated in C. (E) Summary of E-S changes in 3 slices.

Fig 6.

Induction of E-S P and E-S depotentiation requires NMDAR activation. (A and B) d-AP5 (100 μM) blocked LTP induction and E-S P. (C) LTP was first induced by HFS. d-AP5 (100 μM) was applied 20 min before and during 1 Hz stimulation and prevented synaptic depotentiation. (D) Summary of induced changes in E-S coupling.