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 ␥-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.I ntegration of synaptic inputs to produce an action potential at the axon hillock is a complex operation that depends on two critical factors: the distribution of voltage-gated ion channels in the dendrites and the passive electrical properties upon which these active channels are superimposed (1). Synaptic potentials have been shown to be shaped by intrinsic voltage-gated conductances located in the dendrites and the soma (2), but the dynamics of active synaptic integration remains poorly understood. We addressed here the question as to whether synaptic integration is modified after induction of long-term synaptic potentiation and depotentiation.In the area CA1, homosynaptic long-term potentiation (LTP) of excitatory synaptic transmission is induced by high-frequency stimulation (HFS, 100 Hz) of the afferent fibers (3). In parallel, the probability of discharge of the postsynaptic neurons in response to a given excitatory postsynaptic potential (EPSP) is enhanced (4-7). This second component has been called EPSPto-Spike potentiation (E-S potentiation, E-S P) which is complementary to LTP and functionally important. The reversal of LTP preserves a potential for network plasticity and appears essential for any model of memory (8). Long-term synaptic depotentiation has been reported in the area CA1 (9), but the reversal of E-S P has never been clearly established (10, 11). We show here that E-S depression (E-S D) is expressed concomitantly with long-term depression (LTD). E-S D is largely independent of synaptic inhibition but requires N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation for its induction. We provide evidence for an activity-dependent decrease of the intrinsic excitability of CA1 pyramidal neurons that acts in synergy with LTD. MethodsSlice Preparation. Hippocampal slices (400 m) were obtained from 3-to 6-week-old rats according to institutional guidelines. Slices were cut in a solution (280 mM sucrose͞26 mM NaHCO 3 ͞10 mM D-glucose͞1.3 mM KCl͞1 mM CaCl 2 ͞10 mM MgCl 2 ), and were maintained for 1 h at room temperature in oxygenated (95% O 2 ͞5% CO 2 ) artificial cerebrospinal fluid (ACSF; 125 mM NaCl͞2.5 mM KCl͞0.8 mM NaH 2 PO 4 ͞26 mM NaHCO 3 ͞3 mM CaCl 2 ͞2 mM Mg...

Activity-Dependent Long-Term Potentiation of Intrinsic Excitability in Hippocampal CA1 Pyramidal Neurons

“…E-S potentiation has been reported to depend on disinhibition (Abraham et al, 1987;Chavez-Noriega et al, 1990), but later studies have suggested a change in the intrinsic excitability (Wathey et al, 1992;Pugliese et al, 1994;Jester et al, 1995;Wang et al, 2003). More recent studies suggest that full expression of E-S potentiation requires both GABA A receptor-mediated disinhibition and intrinsic potentiation (Daoudal et al, 2002;Staff and Spruston, 2003). The detail mechanisms underlying this form of activity-dependent plasticity are not fully understood.…”

Timing and Balance of Inhibition Enhance the Effect of Long-Term Potentiation on Cell Firing

“…Thus, to understand the computational effects of long-term plasticity, it is necessary to examine the neuronal input-output (I/O) function as a whole. One manner in which the I/O function has been studied is by examining EPSP-spike (E-S) curves in CA1, by plotting the extracellular population spike amplitude as a function of field EPSP (fEPSP) slope (Andersen et al, 1980), or by plotting intracellular spike probability versus EPSP slope (Daoudal et al, 2002;Marder and Buonomano, 2003;Staff and Spruston, 2003). In these studies, the EPSP slope provides a measure of the excitatory component of the synaptic input (Wigstrom and Gustafsson, 1985;McCormick et al, 1993;Pouille and Scanziani, 2001), whereas cell firing provides a measure of the interaction between both excitation and inhibition, which are activated in parallel (Buzsáki, 1984;Pouille and Scanziani, 2001).…”

“…There has been considerable debate as to the mechanisms underlying E-S potentiation, with studies focusing on increased neuronal excitability (Abraham et al, 1985;Taube and Schwartzkroin, 1988;Wathey et al, 1992;Jester et al, 1995;Daoudal et al, 2002) and decreased efficacy of inhibition (Wilson et al, 1981;Abraham et al, 1987;Chavez-Noriega et al, 1989;Tomasulo et al, 1991;McMahon and Kauer, 1997;Lu et al, 2000;Chevaleyre and Castillo, 2003;Staff and Spruston, 2003). There is substantial evidence that a major component of E-S potentiation relies on GABAergic inhibition, because E-S potentiation is mimicked and occluded Chavez-Noriega et al, 1989;Tomasulo et al, 1991;Lu et al, 2000) or reduced (Daoudal et al, 2002;Staff and Spruston, 2003) by GABA A receptor (GABA A R) antagonists (but see Jester et al, 1995;Evans and Viola-McCabe, 1996).…”

“…There is substantial evidence that a major component of E-S potentiation relies on GABAergic inhibition, because E-S potentiation is mimicked and occluded Chavez-Noriega et al, 1989;Tomasulo et al, 1991;Lu et al, 2000) or reduced (Daoudal et al, 2002;Staff and Spruston, 2003) by GABA A receptor (GABA A R) antagonists (but see Jester et al, 1995;Evans and Viola-McCabe, 1996). Several possible explanations exist for the dependence of E-S potentiation on intact inhibition.…”

Excitability changes that complement Hebbian learning

“…During various phases of learning excitability can change dramatically in both cortical and hippocampal networks (Brons & Woody 1980;Moyer et al 1996;Giese et al 2001. ) In vitro studies have revealed changes in both pre-synaptic (Ganguly et al 2000;Li et al 2004) and postsynaptic (Daoudal et al 2002;Xu et al 2005) excitability after LTP protocols. A recent study, however, showed that an increase in the excitability can be induced solely by short periods of high activity, independently of synaptic activation (Cudmore & Turrigiano 2004).…”