Clogged Synapses: better call the mailman (or have a shut eye)

Sleep is fundamental for our brain.

Our ability to learn and memorize new things profits from sleep; and, sleep loss leads to cognitive impairment that can only be reversed by closing our eyes and sleeping1. The more time we spend awake, and the further we engage with learning activities, the more our brains will demand for sleep. 

The synapse is the structure that allows the neuron (or nerve cell) to pass an electrical or chemical signal to another neuron, or to the end effector cell that produces the action demanded from our brain. Synapses are the foundation of neuronal plasticity, and, in the adult brain, synapses can change their strength and size within minutes or hours in response to a new experience and learning1. Recent research has shown that the need for sleep and synaptic function are strongly linked together.

Sarah B. Noya and her colleagues2 from the Institute of Pharmacology and Toxicology of the University of Zürich (Switzerland) have recently shown that 70% of the synaptic transcripts change during our 24h circadian cycles. The transcripts and proteins related to synaptic signaling, accumulate before the active phase of the bodies and get further cleared out during the day.  In the meantime, proteins that are associated with the body metabolism and translation, accumulate in the synapses just before the resting phase or sleeping time. As such, just before we go to bed, the synapses get congested with protein information from our bodies daily function, that needs to be compartmentalized and processed.

We can imagine the synapses as a clerk’s room filling up with boxes and parcels that need to be deliver to the proper address.

But what is interesting, is the result that comes from another study published at the same time, from Franziska Brüning and her team3 at the Institute of Medical Psychology of the Ludwig Maximilian University of Munich (Germany). This research study shows that sleep deprivation abolishes nearly all of the compartmentalization of these accumulating proteins at the synapses (98%); which means that, without a proper shut eye, the synapses get completely clogged with accumulating “protein-parcels” that don’t get removed. When a chemical or electrical information wants to get through the synapses the next day, it can’t because there’s accumulating protein transcripts that haven’t been properly processed, or phosphorylated. The information gets stalled, due to the congestion at the synapses.

So, next time your brain feels fizzle in the morning, and throughout the day; promise yourself (and your brain) to go to bed early, and have a proper night’s rest!



1.         Cirelli C and Tononi G. Linking the need to sleep with synaptic function. Science. 2019;366:189-190.

2.         Noya SB, Colameo D, Bruning F, Spinnler A, Mircsof D, Opitz L, Mann M, Tyagarajan SK, Robles MS and Brown SA. The forebrain synaptic transcriptome is organized by clocks but its proteome is driven by sleep. Science. 2019;366.

3.         Bruning F, Noya SB, Bange T, Koutsouli S, Rudolph JD, Tyagarajan SK, Cox J, Mann M, Brown SA and Robles MS. Sleep-wake cycles drive daily dynamics of synaptic phosphorylation. Science. 2019;366.

Evolution and melatonin

Since life has emerged on Earth, 3.7. billion years ago, the rising and setting of the Sun has been a constant. Whether it was light or dark, it was day or night. Humans, and all other organisms, have evolved with this imposed biological rhythm; and, human physiology was determined by the light/dark cycle.

Every cell in our bodies exhibits a circadian rhythm, a 24h-cycle synchronized to a light/dark pattern. But, how do cells deep inside in our bodies know when it’s dark outside? The answer to that question is Melatonin (N-acetyl-5-methoxytryptamine), the messenger from our brain to communicate to our cells that it is dark. The master clock of the body, the Suprachiasmatic Nucleus (SCN) receives darkness information from the retina and sends it to the brain. From there it provides an input to the Pineal Gland, to produce melatonin. Melatonin secretion increases in the evening, and is stimulated by darkness; whereas light rapidly suppresses melatonin production.

Melatonin is not unique to humans. It is spread through out the animal kingdom, plants, bacteria, and even unicellular organisms have it. There’s no species that has been identified so far that does not contain Melatonin. This expresses the importance of this molecule to life.