Extracellular communication between brain cells through transfer of Cre mRNA

https://www.biorxiv.org/content/10.1101/2023.01.29.525937v1

by arto • 3 years ago

93 14 3 years ago

in situ lentiviral transduction of the striatum of Flox-tdTomato Ai9 mice reporter of Cre activity

ok, now I understand what the scientists that were complaining about the naming of the "'sonic hedgehog' gene" were talking about...

marstall• 3 years ago

yes. I know a bit of neuroscience 101 and the abstract is greek to me. any1 got an ELI5? Sounds like a cool finding.

bglazer• 3 years ago

This isn’t exactly my area of expertise, but I know some of the jargon. Anyways, grain of salt, some details may be incorrect.

Brain cells, and many other cell types communicate by releasing vesicles, which are very small bubbles of the cell’s membrane. These vesicles contain cargo, proteins or RNA, which generally function as signals of the cell’s state. These authors have engineered a pretty clever system for tracking when brain cells exchange these vesicles.

First they insert two genes into mice. The first is called tdTomato and is a red fluorescent protein. Crucially, they insert this gene backwards. I’ll explain that in a second. Directly on either side of this gene, they also include a specific section of DNA called a LoxP site. This LoxP site is recognized by a protein called Cre. Cre binds to two LoxP sites, pulls them together, cuts out the DNA between them, flips the direction of the DNA, then reinserts it backwards. So, normally the backwards tdTomato can’t be expressed as a protein, but if Cre protein is introduced, it will flip the tdTomato and suddenly the cell will start generating this red fluorescing protein.

The authors also engineered a virus to carry the Cre protein. Specifically they chose a lentivirus, which inserts its own genome into its host’s genome. Here this means the virus inserts the DNA encoding the Cre protein. They injected this virus into one area of the mouse brain, the striatum. Now the striatum cells express Cre, flip the tdTomato, and glow red. The lentivirus is not capable of expanding, so it stays isolated to the injection site in the striatum.

But, the most important part is that the striatum cells also sometimes package up Cre mRNA in their vesicles. They export those vesicles and other brain cells take them up. Then those other brain cells express the Cre, and as a result, glow a pleasing 581nm wavelength red. This tells the authors that red glowing cells received a vesicle from a cell in the striatum.

Very clever! As on example of an application, this could help scientists better understand how brain tumor cells are affecting other cells in the brain through vesicles.

phendrenad2• 3 years ago

Neurons communicate via light (maybe), neurons communicate via mRNA (maybe), what's next? Neurons communicate via sound?

suby• 3 years ago

what's next? Neurons communicate via sound?

Certainly, but the neurons communicating via sound is to neurons in external brains.

Terr_• 3 years ago

Indeed, that case is frequently taken for granted and overlooked.

However there is another scenario that is considered even less, when the sound signal is going back to the same brain for reprocessing.

Sometimes intermediated by a small yellow rubber duck.

amelius• 3 years ago

You forgot hormones.

mimd• 3 years ago

They was some debate and research over mechanical pulses in axons a few years ago. Not sure what's the status of it.

I would like to find the bounds on the "bits" communicated between neurons, so I could then calculate the throughput of the eye for example. Helps to put bounds/identify the algorithms/processing for CV. However, I kept running into increasing complexity/unknowns over the general (and increasingly simplistic) theory of neuro communication and just general unknowns about the dendrite to axon terminal process and all the post signaling cascades.

Sigh, it's a fascinating area.

Kiboneu• 3 years ago

Nature tends toward heterogeneity of physical channels for signalling, as opposed to engineered systems which normally dedicate one channel (electricity) at a time for all signals (and when they accidentally do not we call it a "side-channel").

The heterogeneity provides noise resistance from the environment and a physical priority/filter system for signals necessary for an organism's survival.

These physical channels provide upper bounds for the richness, latency and diffusion of the information; they also incur different costs for maintenance and usage. In turn, evolutionary selection of organisms will yield signalling channels for pain, navigation and other signals necessary for survival within a short time-frame towards fast channels like an electric charge emitted and relayed / filtered by neurons (cells appear to also be affected by charge distributions throughout bodies of certain organisms, which affects limb / organ regeneration; but that's not a charge signified by rapid state changes as one would find in a neuron). Faster responses are made-up for by predictive / reflexive circuits. Slower signals tend to be chemical or mechanical in nature. Chemical messengers diffuse throughout the body better because they can travel with the bloodstream, and trigger all sorts of metabolic machinery for energy availability in /anticipation/ of danger (in exchange for internal damage and reduced immune response).

There are also a multitude of non neural cells that support neural cells in the brain, structurally and by providing resources. Neurons move about a lot, so there is certainly a lot of mechanical activity which might create a small amount of sound in some localized area of brain matter. If that is the case, and if that sound can be isolated as a signal event which in turn becomes useful for constructing neural circuitry, then yeah I would not be surprised if there was an acoustic communication channel as well.

mRNA has been suspected as an information channel between neurons for a while, I think.

The principle is that life is information's way of folding itself into the appropriate substrates. The "appropriate substrates" are physical mediums that survive the environment longer and better than lesser appropriate substrates.

Extracellular communication between brain cells through transfer of Cre mRNA

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