Excitatory postsynaptic current

Figure 13.3 Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) from dorsal horn neurons of rat (prenatal P2-13) spinal cord slices. The normal evoked EPSC of about 160pA obtained by focal stimulation of nearby tissue was dramatically reduced by addition of a cocktail (CABS) of CNQX 10 pM, D-APV 50 pM, bicuculline 10 pM and strychnine 5 pM to block glutamate, GABAa and glycine receptors. The small residual EPSC shown was blocked by the ATP P2 receptor antagonist suramin and is therefore probably mediated by released ATP. (Prom Bardoni et al. 1997 and reproduced by permission of the Journal of Neuroscience)...

SSR-504734 is a potent, selective, and reversible inhibitor (IC50 = 18 nM) that is competitive with glycine [47,51]. The inhibitor rapidly and reversibly blocked the uptake of [14C]glycine in mouse cortical homogenates, which was sustained for up to 7 h. Complete cessation of blockade and return to glycine basal levels occurred prior to 24 h, which is in stark contrast to NFPS (>24 h). SSR-504734 potentiated a nearly twofold increase of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in rat hippocampal slices and produced an increase in contralateral rotations in mice when microinjected into the striatum. Microdialysis experiments indicated that the inhibitor induced a rapid and sustained increase in extracellular glycine levels in the PFC of freely moving rats [51]. The compound also demonstrated efficacy in a variety of psychosis models [51-53]. SSR-504734 was reportedly in clinical trials for schizophrenia but discontinued after Phase I (data not disclosed) [54]. 

Yamada, K. A. and Rothman, S. M. (1992) Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons. J. Physiol. 458, 409 123. 

Y receptors in the rat spinal cord a direct effect on the vesicle release machinery (step 4 in Figure 3) can be assumed, since agonists inhibited the frequency of the miniature inhibitory or excitatory postsynaptic currents (Moran et al. 2004 italics in Table 3). 

At the calyx of Held in the medial nucleus of the trapezoid body, activation of presynaptic glycine receptors was also shown to facilitate spontaneous glutamate release and to enhance amplitudes of evoked excitatory postsynaptic currents (Turecek and Trussell 2001). The action on spontaneous postsynaptic currents were insensitive towards a blockade of Na+ channels by tetrodotoxin, but abolished by the Ca2+ channel blocker Cd2+. This indicated that glycine acted by causing a depolarization, which was also corroborated by direct voltage measurements. 

However, presynaptic NMDA autoreceptors may also mediate opposite effects, i.e., a reduction of glutamate release. At parallel fiber Purkinje cell synapses, activation of presynaptic NMDA receptors caused significant reductions in excitatory postsynaptic currents (Casado et al. 2002). Likewise, spontaneous and evoked glutamate release from the nerve endings of primary afferents in the spinal cord was reduced when presynaptic NMDA receptors were activated (Bardoni et al. 2004). In contrast to this, substance P release at such synapses was shown to be enhanced by the activation of presynaptic NMDA receptors (Liu et al. 1997). 

In the hippocampus, presynaptic P2X2 receptors mediated increases in the frequencies of miniature excitatory postsynaptic currents in stratum radiatum intemeu-rons, but not in pyramidal neurons (Khakh et al. 2003). Glutamate release from hippocampal mossy fibers, in contrast, was found to be inhibited by P2X7 receptor activation (Armstrong et al. 2002). 

Studies on 5-HT2A-Induced Spontaneous Excitatory Postsynaptic Currents... 

Fig. 4. Electrophysiological traces from a prefrontal layer V showing the response to nearby electrical stimulation of corticocortical afferents. Stimulus artifact appears as a vertical line. (1) The fast evoked excitatory postsynaptic current (evEPSC) follows immediately, as depicted by the arrow. Under normal conditions, stimulation at 0.1 Hz evokes only a fast evEPSC. (2) However, after the application of a psychedelic hallucinogen (3 pMDOI, 15 min), stimulation at this frequency almost always evokes both a fast evEPSC and a late evEPSC, as depicted by the arrows. The neuron is voltage-clamped close to its resting potential and was not directly depolarized by DOI. It is not known what type of glutamate release accounts for the late evEPSC. Traces are averages of 10 sweeps taken during each of the conditions.

Marek GJ, Aghajanian GK. 5-HT2A receptor or a,-adrenoceptor activation induces excitatory postsynaptic currents in layer V pyramidal cells of the medial prefrontal cortex. Eur J Pharmacol 1999 367 197-206. 

Umemiya M, Raymond LA (1997) Dopaminergic modulation of excitatory postsynaptic currents in rat... 

Knock-down of kalirin-7 levels reduces basal spine density and the frequency of miniature excitatory postsynaptic currents (mEPSCs) (Xie et al., 2007). Also, kalirin has been linked to the EphB receptor. Activation of the EphB receptor by ephrin-B has been shown to translocate kalirin-7 to synapses where it locally... 

An example of a whole cell study is shown in Fig. 2b. Excitatory postsynaptic currents (EPSCs), which are caused... 

EPSC excitatory postsynaptic currents are the flow of ions resulting in EPSP... 

Synaptic and extrasynaptic receptors may also differ in their subunit compositions. The kinetics of NMDA excitatory postsynaptic currents (EPSCs) become faster during development in the CNS and correlate with an increase in expression... 

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