Hi!

Both events - sE(I)PSCs and mE(I)PSCs are similar in the fact that they occur without any artificial stimulation. The difference between sE(I)PSCs and mE(I)PSCs is coming from the fact that in case of the sE(I)PSCs there is a chance of action potential-driven events due to intrinsic properties of presynaptic cell and/or network activity. All the mE(I)PSCs, in turn, are recorded in the presence of tetrodotoxin (TTX) which blocks action potential formation and its propogation, thus mE(I)PSCs are more "spontaneous" events than sE(I)PSCs and can be further used for the quantification of readily releasable pool size. So, it is useful to take both  sE(I)PSCs and mE(I)PSCs  from the same cell. First, one can record the sE(I)PSCs and then, by introducing TTX into bath solution the mE(I)PSCs. Having both sE(I)PSCs and mE(I)PSCs can help to understand where the changes in synaptic trasmission are coming from. Whether it is from the presynaptic side, or postsynaptic or both.

Best,

Miroslav

Hi!

Both events - sE(I)PSCs and mE(I)PSCs are similar in the fact that they occur without any artificial stimulation. The difference between sE(I)PSCs and mE(I)PSCs is coming from the fact that in case of the sE(I)PSCs there is a chance of action potential-driven events due to intrinsic properties of presynaptic cell and/or network activity. All the mE(I)PSCs, in turn, are recorded in the presence of tetrodotoxin (TTX) which blocks action potential formation and its propogation, thus mE(I)PSCs are more "spontaneous" events than sE(I)PSCs and can be further used for the quantification of readily releasable pool size. So, it is useful to take both  sE(I)PSCs and mE(I)PSCs  from the same cell. First, one can record the sE(I)PSCs and then, by introducing TTX into bath solution the mE(I)PSCs. Having both sE(I)PSCs and mE(I)PSCs can help to understand where the changes in synaptic trasmission are coming from. Whether it is from the presynaptic side, or postsynaptic or both.

Best,

Miroslav

Hi Mirsolav,

Thank you very much for your clear explanation, I understand the difference now! 

Regards,

Julie

In their original observations with miniature synaptic potentials at the frog neuromuscular junction, Fatt and Katz (1952) referred to them as 'miniature spontaneous end plate potentials, and the subsequent terminologies "spontaneous epsps" or "miniature epsps" are often used interchangeably. Under some physiological conditions, such as in saline solution with a low concentration of calcium ions, evoked epsps are reduced in amplitude and waveform to the same values as the spontaneous miniature epsps, hence while under those conditions the two events resemble one another in both amplitude and time course, they are technically different. Ultimately the membrane events leading to release of quanta of synaptic transmitter are identical in the two instances, however; it's just that the arrival of pre-synaptic action potentials at the synapse raises the probability of quantal release.

Fatt, P. and Katz, B. 1952. Spontaneous subthreshold activity at motor nerve-endings.

J. Physiol. 117:109-128.

You should also know that when reading about and/or examining mE(I)PSCs, you should be able to decipher presynaptic from postsynaptic events. The frequency of the mPSC is dependent upon vesicular release whereas the amplitude of the mPSC is dependent upon activation of the postsynaptic receptor. As an example, if you see a reduction in the frequency of mIPSCs, it is due to a decrease in the release of GABA, while a decrease in the amplitude of mIPSCs is due to reduced activation of postsynaptic GABAA receptors. 

Thank you Eric for the useful information!

Regards,

Julie

Eric,

You are largely correct. There is an unusual exception to this rule, however. A drug referred to as hemicholinium interferes with the re-uptake of choline at the vertebrate neuromuscular junction; prolonged exposure to hemicholinium leads to a gradual reduction in the amplitude of the miniature end plate potentials, even though the site of action is at the (presynaptic) motor terminals.

Elmquist, D., Quastel, J.M., Thesleff, S. 1963. Prejunctional action of HC-3 on neuromuscular transmission. J.Physiol. 167:47-48 P. 

.

Hi Deforest. Thank you, that is very interesting. You are correct, the authors of this paper did state that there is gradual reduction in the amplitude of mEPPs. However, they also found reduced quantal size, since the uptake of choline was impaired. In these conditions, however there was constant electrical stimulation. So while there is a presynaptic effect, contributing to reduced frequency, would you think that the decrease in amplitude may be due to desensitization of postsynaptic ACh receptors? The reason I believe it may be due to desensitization is because without stimulation, there is no change in quantum or mEPP size with time and an accumulation of ACh at cholinergic synapses often leads to desensitization of the receptors. 

Hi Eric,

While I am not an expert on synaptic desensitization, your suggestion certainly has a great deal of merit. Without a corresponding decrease in amplitude of spontaneous mEPPs in unstimulated preparations exposed to hemicholinium, I would have to agree with your explanation. Good point! 

Eric, a reduced mI/EPSC frequency also reflects a reduction in the number of functional synapses, not just a change in the pre-synaptic release probability. 

I got interested in this question recently and did a little research. Here are some citations to back up what everyone said above. 

1. A study of sEPSC and mEPSC in the prefrontal neurons shows that they have similar characteristics:

" In the present work, we investigated the possibility of using the characteristics of spontaneous excitatory postsynaptic currents (EPSCs) for estimation of quantum parameters of excitatory synaptic transmission in different types of neurons from rat prefrontal cortex slices. By blocking spontaneous spiking activity in slices by tetrodotoxin, we showed that spontaneous and miniature EPSCs in the prefrontal cortex neurons did not differ in their properties. Therefore, both spontaneous and miniature responses can be used for estimation of quantum parameters of excitatory synaptic transmission in this preparation. " [1]

2. A detailed discussion of the amplitude and frequency of mEPSC:

"Increases in mEPSC amplitude are consistent with higher density/conductance of postsynaptic receptors at individual synapses [23]. Elevated mEPSC frequency is usually interpreted as increases in either the presynaptic release probability at existing sites (increases in the vesicular pool or vesicular turnover rate) [29] or in the number of functional synaptic sites (more dendritic spines or new synapses onto already established spines) [30]. ... However, caution is needed in attributing mEPSC alterations to exclusively pre/postsynaptic changes. For instance, mEPSC frequency and amplitude are not independent; practically speaking, once synapses become very small, current amplitudes from them fall below the threshold of detection and this leads to a decrease in the measured frequency. Additionally, unsilencing of so-called “silent” synapses that previously lacked AMPARs [30] is a postsynaptic effect which manifests as a change in mEPSC frequency. Furthermore, there is evidence that pre- and postsynaptic development is coordinated [31, 32]. " [2]

[1] Malkin, S.L. et al. (2014) Properties of Spontaneous and Miniature Excitatory Postsynaptic Currents in Neurons of the Rat Prefrontal Cortex. Comp. Ontog. Physiol. 50, 506–514

[2] Queenan, B.N. et al. (2012) Wherefore art thou, homeo(stasis)? Functional diversity in homeostatic synaptic plasticity. Neural Plast. 2012, 718203

following this question: what is exactly the TTX-sensitive component of the sEPSC? Can I say that the TTX-sensitive part is sodium currents, and TTX-insensitive part is calcium current?

Jingda,

The conventional wisdom is that sEPSP are not evoked events and therefore, being independent of motor nerve action potentials and their voltage-sensitive sodium channels, should be unaffected by TTX. Most voltage-gated calcium channels are not sensitive to TTX either. If you are seeing an effect of TTX, then the EPSPs you are working with may actually be evoked by presynaptic nerve activity.

For me, the best description of the difference between sPSCs and mPSCs is as follows:

"Spontaneous postsynaptic currents are currents generated by action-potential-dependent and –independent release of neurotransmitter in the absence of experimental stimulation. Miniature postsynaptic currents are currents observed in the absence of presynaptic action potentials; they are thought to correspond to the response that is elicited by a single vesicle of transmitter." (1)

1. Pinheiro, P. S. & Mulle, C. Presynaptic glutamate receptors: physiological functions and mechanisms of action. Nature reviews. Neuroscience 9, 423-436 (2008).

Note: came from the glossary of this article.

Thank you Eamonn, very clear definitions! 

Julie

May I ask two questions here:

1, Do mEPSCs and sEPSCs looks same using voltage clamping? Can we tell their difference by their amplitude or halfwidth?

2, For mEPSCs of very small amplitude, how to confirm they are not background noise?

thank you.

Hi Geng,

1, As far as I know, mEPSCs and sEPSCs look the same, the only way we can tell them appart is that mEPSCs remain after adding tetrodotoxin.

2, mEPSCs of very small amplitude may be confound with background noise. In this type of analysis, it is sometimes necessary to do all that is possible to reduce noise (improve grounding, disconnect fluorescence,...) or you may not be able to see the mEPSCs.