When an electric signal reaches a chemical synapse, the signal is transmitted using neurotransmitters. Afterwards, the neurotransmitters are removed from the synaptic cleft. My question is whether it happens in a normally functioning brain that neurotransmitter concentrations in the synaptic cleft add up if there are several impulses in quick succession? If so, does this serve any purpose? Or is the time between two impulses always long enough for all of the neurotransmitter to be removed from the synaptic cleft?

Edit: To further clarify (as the currently only answer does not really adress my issue), I am aware of the principle of summation, however I do not know whether this is actually caused by multiple neurotransmitter emissions "adding up" in the synaptic cleft or whether the postsynaptic membrane can just somehow remember if there was an increased amount of neurotransmitter recently.

To describe it graphically: According to this article, the concentration of serotonin in the synaptic cleft during a single impulse looks somewhat like that. Now when there is a quick series of impulses, does the neurotransmitter always get removed before the next impulse as on the right side of the following image, or can it add up as on the left side? And if it does add up, does this actually serve the purpose of temporal summation or some other purpose?

5HT in the synaptic cleft)

  • $\begingroup$ I think as bpedit said the temporal summation also occurs at the body of the neuron as well as at the synapse, although I do expect that your left hand image will represent the concentrations if the APs follow each other close enough by overloading the transport mechanisms. $\endgroup$
    – Anon
    Oct 28, 2016 at 4:22

2 Answers 2


The answer by bpedit is a good explanation of temporal/spatial summation, which can be partly a postsynaptic phenomenon (due to membrane time constants or second messenger sytems, for example).

Your specific question is about whether extracellular neurotransmitter levels sum over time. This definitely occurs regularly with "neuromodulatory" neurotransmitters like serotonin (others that behave similarly include dopamine and norepinephrine/epinephrine). "Faster" neurotransmitters like glutamate and GABA are cleared more quickly, though there are complicating factors there as well that are outside the scope of this question.

Although the summation has been shown many times, I looked quickly for an example and found the paper by Bunin and Wightman, 1998. Figures 2-6 all show extracellular serotonin concentrations that are elevated for seconds after release (let me know in the comments if you can't access this paper at your institution), and they show the changes in extracellular concentrations with multiple stimulus pulses (see in particular Figure 3).

  • $\begingroup$ Thanks, something like the figures in the quoted paper was just what I was looking for! $\endgroup$
    – vauge
    Nov 3, 2016 at 11:17

The addition of multiple impulses is termed summation and is instrumental in whether an action potential will be induced in the post-synaptic neuron. If the neurotranstitter released by one action potential in the pre-synaptic neuron was enough to cause an action potential in the post-synaptic neuron, the whole idea of neruotransmitters would be a waste of energy and resources. In these circumstances an electrical synapse would suffice, the chemical synapse being "overkill".

Temporal summation happens when several action potentials arrive in quick succession from a particular neuron. Spacial summation occurs when action potentials arrive from multiple neurons, at roughly the same time, to act on a localized area of a post-synaptic neuron. In either case, the effect of a single action potential is not enough to cause a large enough influx of ions to initiate a new action potential, whereas the combined effect of several action potentials is enough to reach the threshhold value necessary.

There can also be inhibitory contributions to this process as well. These typically increase the resting membrane potential making it harder to reach the threshold needed to initiate an action potential. All-in-all it's rather like a voting process that occurs at the synapse (or small region of multiple synapses). This "voting" allows for complex integration of all the inputs neurons receive.

Here's what appears to be a good reference on summation: https://www.ncbi.nlm.nih.gov/books/NBK11104/

Here's the Wiki link as well: https://en.wikipedia.org/wiki/Summation_(neurophysiology)#Temporal_summation

Here's an instructive video, I've only watched a couple minutes but it appears a reasonable visual treatment: http://www.interactive-biology.com/1660/what-is-summation-2-types-episode-19/

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    $\begingroup$ Some of the information contained in this post requires additional references. Please edit to add citations to reliable sources that support the assertions made here. Unsourced material may be disputed or deleted. $\endgroup$
    – MattDMo
    Oct 24, 2016 at 17:35
  • $\begingroup$ This is all right out of any introductory Biology textbook, stuff I've taught for over 20 years. All easily verifible online, hundreds of thousands of hits. With what particularily do you have an issue? $\endgroup$
    – bpedit
    Oct 24, 2016 at 17:44
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    $\begingroup$ You may be familiar with the material, but that doesn't mean everyone else is. I'm an immunologist, and I know the difference between T and B cells, but I always include links to Wikipedia when I mention them here because others may not know, or may simply be interested in learning more. I could not cite them with the excuse that "it's all easily verifiable online", but you could say the same about every citation in a primary research paper. I highly recommend reading completely through this Meta discussion regarding citations. $\endgroup$
    – MattDMo
    Oct 24, 2016 at 17:59
  • $\begingroup$ Just to be sure: the summation is not only caused by the fact that the postsynaptic membrane somehow remembers that there was an increased amount of neurotransmitters shortly before the second impulse, but that there actually still is neurotransmitter left from the first impulse in the synaptic cleft? $\endgroup$
    – vauge
    Oct 24, 2016 at 18:02
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    $\begingroup$ @vauge - Both, in a way; there can be residual neurotransmitter in the synaptic cleft, and there can be neurotransmitter that remains bound to receptors (you could possibly think of this as 'memory'). Finally, to add to bpedit's comment, your question referred to serotonin, and most serotonin receptors are g-protein coupled receptors; g-protein receptors subsequently affect second messenger systems like cAMP and IP3/DAG whose effects remain over long time scales, seconds and longer. $\endgroup$
    – Bryan Krause
    Oct 28, 2016 at 20:54

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