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 throughput the day; promise yourself (and your brain) to go to bed early, and have a proper night’s rest!

Compartmentalization of your synapses
Compartmentalization!

References:

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.

Habenula, the Master of the Brain

The Habenula, is an area of our brains close to the pineal gland, that is involved in pain processing, reproductive behaviour, nutrition, sleep-wake cycles and stress responses, among other things1. A professor I used to know always said the Habenula was the Master of the Brain… and, indeed, recent research has provided evidence that this tiny bundle of nerves is able to produce Dimethyltryptamine (DMT), a psychedelic drug, “cousin” to the famous LySergic acid Diethylamide (LSD). 

DMT is internally bio-synthesized by the enzymes Aromatic-L-Amino acid DeCarboxylase (AADC) and Indolethylamine-N-Methyltransferase (INMT). Dean and colleagues2 were able to identify INMT messenger RNA in human tissues, by using a RNAscope in situ assay system; a highly sensitive technique, which proved for the first time a clear-cut identification of DMT and its enzymes in human brain. 

Outstanding, was the discovery that there was a significant increase of DMT levels in the rat brain after stimulation of experimental cardiac arrest; showing for the first time, that the brain is capable of synthesizing and releasing DMT under stress. 

This ultimately raises the possibility that this phenomenon may also occur in human brains, when we experience situations of extreme stress. The researchers attest that the cardiac arrest-induced increase of DMT may be related to “near-death experiences”, as reported by Timmermann and collegues3. This group recently reported that human subjects given exogenous DMT, experienced “near-death”-like mental states, including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with ‘entities’, and themes related to death and dying.

It’s unbelievable that the more we know about how our body and brain functions, the more I realize that our mind is a construction of our organic biological nature.

What we sometimes perceive as a mystical experience is probably just rooted in an organic mechanism that is tricking our minds into a “trip”.

Into the light

References:

1.         Namboodiri VM, Rodriguez-Romaguera J and Stuber GD. The habenula. Curr Biol. 2016;26:R873-R877.

2.         Jon G. Dean TL, Sean Huff, Ben Sheler, Steven A. Barker, Rick J. Strassman, Michael M. Wang & Jimo Borjigin Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain. Scientific Reports. 2019;9.

3.         Timmermann C, Roseman L, Williams L, Erritzoe D, Martial C, Cassol H, Laureys S, Nutt D and Carhart-Harris R. DMT Models the Near-Death Experience. Front Psychol. 2018;9:1424.