Voltage dependence of excitatory postsynaptic potentials of rat neocortical neurons

Abstract

1. The properties of excitatory postsynaptic potentials (EPSPs) of rat neocortical neurons were investigated with a fast single-electrode current-voltage clamp in vitro. Typically, apparently pure EPSPs were obtained by selection of electric stimuli of low intensity. 2. The amplitude and time integral of the EPSP increased when the neuron was depolarized. At threshold for generation of action potentials, the amplitude of EPSPs was increased by approximately 30% [from 5.0 +/- 2.1 to 6.3 +/- 1.0 (SD) mV, n = 12]. The integral of EPSPs was maximally about fourfold (3.7 +/- 1.5, n = 16) larger than at resting membrane potential (Em). The mechanisms involved in this augmentation of EPSPs were further investigated. 3. The amplitude and the time integral of excitatory postsynaptic currents (EPSCs) decreased linearly with shifts in command potential from -100 to -60 mV. The decrease of the EPSC integral with depolarization indicates that the enhancement of the EPSP may be brought about by recruitment of a voltage-dependent inward current. 4. Evoking EPSPs at various delays after the onset of small depolarizing current pulses (0.3-0.6 nA, 600 ms) revealed that augmentation decays with time. The integral of EPSPs evoked approximately 80 ms after the onset of the current pulse was 3.7 (+/- 1.5, n = 16) times larger than at Em. The integral of EPSPs evoked at 480 ms. however, were only twofold (+/- 0.7, n = 16) larger. Hence EPSPs evoked after a delay of 80 ms were 1.7-fold (+/- 0.4, n = 24) larger than EPSPs evoked after 480 ms. EPSCs were independent of the delay of stimulation at all potentials. 5. Intracellular application of the lidocaine derivative N-(2,6-dimethyl-phenylcarbamoylmethyl) triethylammonium bromide (QX 314) at 100 mM from pipettes rapidly abolished fast action potentials and inward rectification. During comparable depolarizations the increase in EPSP integrals was much smaller in QX 314-treated neurons than in controls. On average, the integral of EPSPs evoked at 70-90 ms was 1.7 times (+/- 1.0) larger than at Em, and the integral of EPSPs evoked with larger delays was close to the value obtained at resting Em (0.9 +/- 0.3, n = 8). The ratio of EPSP integrals early versus late (1.8 +/- 0.5) is comparable to controls, suggesting that QX 314-sensitive currents are unlikely to be involved in the time-dependent enhancement. 6. Mimicking EPSPs by brief depolarizations atop long depolarizations revealed a time- and voltage-dependent enhancement comparable to that of EPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of negative conductances in neuronal subthreshold properties and synaptic integration

“…Blocking NMDA currents with AP5 did not affect substantially the EPSP (Deisz et al 1991;González-Burgos and Barrionuevo 2001;Hirsch and Gilbert 1991;Stuart and Sakmann 1995;Thomson et al 1988). However, the effect of NMDA currents in some other areas appears to be more significant.…”

“…It is known that the amplitude and duration of EPSPs are voltage dependent and that depolarization of the membrane potential to values close to action potential threshold amplifies the EPSP amplitude and prolongs its decay phase (Deisz et al 1991;Thomson et al 1988;Zsiros and Hestrin 2005). Experiments using sodium and calcium blockers in the perfusion bath could be performed in order to determine whether these postsynaptic conductances are responsible for this effect, but since these blockers also impair glutamate release by the presynaptic fiber it is complicated to assess their effect on the EPSPs.…”

“…Experiments using sodium and calcium blockers in the perfusion bath could be performed in order to determine whether these postsynaptic conductances are responsible for this effect, but since these blockers also impair glutamate release by the presynaptic fiber it is complicated to assess their effect on the EPSPs. Several approaches have been considered to circumvent this limitation, such as the injection of artificial EPSCs directly into the postsynaptic neuron (Stuart and Sakmann 1995;Ceballos et al 2017), local application of sodium or calcium blockers to the postsynaptic neuron (González-Burgos and Barrionuevo 2001;Stuart and Sakmann 1995) and the use of intracellular sodium channel blockers, such as QX 314 (Deisz et al 1991;González-Burgos and Barrionuevo 2001). Recently, more advanced techniques have been used, such as glutamate uncaging (Carter et al 2012;Liu and Shipley 2008) or knockout animals of Na v channels (Branco et al 2016).…”

“…The amplification of EPSPs by I NaP has been extensively observed in neurons from the neocortex (Andreasen and Lambert 1999;Carter et al 2012;Deisz et al 1991;Fricker and Miles 2000;González-Burgos and Barrionuevo 2001;Hirsch and Gilbert 1991;Lipowsky et al 1996;Rotaru et al 2007;Schwindt and Crill 1995;Stafstrom et al 1985;Stuart and Sakmann 1995;Thomson et al 1988;Zsiros and Hestrin 2005), hippocampus (Ceballos et al 2017;Urban et al 1998;Vervaeke et al 2006), entorhinal cortex (Economo et al 2014;Rosenkranz and Johnston 2007), dorsal cochlear nucleus (Hirsch and Oertel 1988), subthalamic nucleus (Farries et al 2010), hypothalamus (Branco et al 2016), olfactory bulb (Liu and Shipley 2008), dorsal horn of the spinal cord (Prescott and De Koninck 2005), medial superior olive and substantia nigra pars compacta (Yamashita and Isa 2004). In most of these experiments, blocking I NaP with TTX abolished the voltage dependence of the EPSP amplitude and area.…”

“…Thomson et al (1988) showed that the amplitude and duration of EPSPs are voltage dependent and that depolarization of the membrane potential to values close to the action potential threshold amplifies the EPSP amplitude and prolongs its decay phase. It was subsequently established that these effects are mediated mainly by I NaP (Andreasen and Lambert 1999;Deisz et al 1991;Lipowsky et al 1996;Schwindt and Crill 1995;Stuart and Sakmann 1995;Urban et al 1998). Voltagedependent calcium currents (I Ca ) can similarly produce these effects (Gillessen and Alzheimer 1997).…”