The Meaning of Life and Other Vegetables

Hello everyone.

Picking up from here (or here, or here) –

One of the most prevalent metaphors used in current-day popular neuroscience is Rewiring. Prevalent, but quite misleading in my opinion.

I understand the difference between literal and figurative, between precision and metaphors. I do. But metaphors exist for a reason. They exist to distill or highlight something, to convey some salient point(s), while discarding (or deviating from) a part of the full, correct picture, which is not essential in a given context. That’s useful. However, when a metaphor take on a life of its own, when it overrides the thing(s) it initially related to, when we start thinking about it as a literal representation – it becomes detrimental to understanding.

“Rewiring” implies a baseline “wiring” situation. Remember, we’re talking about the nervous system. About nerve cells and how they connect. “Wiring” comes from the electrical world (duh). In that world, the wires are most commonly made of copper – solid core or thin-stranded, but essentially copper wires (or the likes). Well then, what are the characteristics of copper wires?

– They are solid and quite resilient, mechanically.
– They can be flexibly bent, and then retain their new shape.
– They can be cut and spliced, including branching out.
– Most important: They can be connected via soldering, creating a mechanical-and-signal connection.

Neurons are definitely different in all the above senses!

Are they solid and mechanically-resilient? Absolutely not. They are more paste-like, and will severe (or at least badly damage) at the slightest mechanical challenge.

Yes, they can be “flexibly bent” (as routinely happens inside your body; but when the bending is external and just a bit too violent, it might be too much for them); they certainly don’t retain their new shape like copper wires do.

Can they be cut and spliced? Cut – for sure. Spliced – not that we know how to, reliably. I guess cutting edge techniques exist / are being developed, but it’s nothing like the straightforward splicing of copper wires: Strip the insulation, twist together, tin if you wish, heat shrink for a neat finish – easy, quick, reliable. Another interesting question relates to branching the signal connection. Can neurons branch out? Latest evidence indicates that yes, sometimes they might branch out. But that takes very specific circumstances, and they probably don’t branch out from any point along their length. As far as I know, we currently can’t branch them out by direct intervention, but maybe I’m just not up to date.

Last on the comparison list, and probably this is where “Rewiring” is most damaging to our understanding – not only neurons can’t be “soldered” to create a mechanical-and-signal connection, they connect in a completely different manner to electrical wires. The connection between every two neurons is chemical, not electrical, and there is actually a physical gap between them – the Synapse.

In an electrical connection, the electrons travel through the substrate, or at least the electrical potential is communicated via substrate continuity (of course, there is also wireless communication, which doesn’t require that; but no one seems to talk about “wireless” in neuroscience). In our nervous system, the signal crosses over between two neurons not via an electrical current or potential (voltage) travelling through, but via molecules – the neurotransmitters – which are released from one neuron’s “end”, then land on and attach to receptors on the other neuron’s “antenna” (the dendrite). It is indeed a very tiny gap, which facilitates fast communications, but the neurotransmitters nonetheless need to “swim across” to get there.

So, the nature of the connection between two neurons is VERY different from an electrical wiring connection, and it has many implications. My point? That talking about neural connections, disconnections and communications in terms of “wiring” (or “rewiring”) is quite misleading, in that light. Perhaps not in all contexts; perhaps in some specific instances it can still be a useful metaphor. But I feel that in the general popular-science speech it’s distracting, rather than illuminating.

I understand that when it comes to signal travel along a single neuron (more specifically, along the exon), and maybe also to how potential is built up in the dendrites until the neuron “fires”, the “wiring” metaphor is more appropriate. After all, in those contexts it IS about the buildup and travel of electrical potential along “a sort of a wire”. I guess that’s where the metaphor was born, and maybe in that narrow context it’s still illuminating. However, outside that domain I believe the current, prolific use of “rewiring” is not helping build a fairly-accurate layman-level understanding of how the nervous system works.

So far I’ve talked more generally about the applicability of the “wiring” metaphor to the nervous system. But what triggered this post is “Rewiring” in specific. What are we taking about, then? If you pick a random popular-neuroscience talk on YouTube (and sadly, these days some peer-reviewed scientific papers too), you’ll notice that “Rewiring” (or even just “wiring”) is used in relating to the strength of the synaptic connection. Perhaps the most popularised expression illustrating this is “Fire together, wire together“, which, on a layman level, means: When a signal gets across a specific synaptic gap (= a signal arrives through the upstream neuron and subsequently the downstream neuron fires), that synaptic connection strengthens. I’m not disputing the insight; only the way it’s talked about.

What is – actually – happening there?

First, we need to ask ourselves: Do we even know, fully and exactly, what is happening there?… As far as I can see – No, we don’t. But assuming we know enough about it to discuss the mechanism, or the system, intelligently –

The signal is transferred across the synaptic gap via the release (on one side) and reception (on the other) of neurotransmitter molecules. The way we currently understand neuron firing mechanisms, such firing requires the buildup of potential (through accumulation of stimulation) in the dendrite(s), past a threshold. Every time a neurotransmitter molecule lands in / attaches to a receptor on a dendrite, it contributes something to that buildup. More such “landings” = more stimulation = closer to crossing the threshold and downstream firing.

Now, let me make it a bit more explicit than I already (over?)did. A bit more pedantic, haha. [I recently read a great blogpost which argued that blogging is all about stating the obvious.] What exactly is meant in saying that “the synaptic connection strengthens”? In my understanding, it means that less stimulation is required for triggering downstream firing. The connection’s “quality” (or strength) can be thought of as “less stimulation is lost across the gap” (Warning: this is just a useful metaphor, and science tells us it actually works a little differently.) Strong connection = easy flow of stimulus. Weak connection = need to work “harder” (or longer) to get the message across.

So, what does current science actually tell us about that? It tells us that more-potential-at-the-dendrite-per-upstream-signal (which would amount to an easier flow of stimulus) happens in two ways. The first is that the axon somehow releases more individual neurotransmitter molecules per action (=arrival of signal along that axon). Discussing how exactly this happens feels like already too much for this post (and it actually doesn’t matter too much for the point I’m making here today). The other way is that the dendrite on the other side of the same gap somehow develops more receptors for that specific neurotransmitter, so there are more of them, maybe many more, “open for business”. [As an aside, the opposite apparently happens when the connection is less active – the dendrite “loses” receptor sites, making the connection less potent.]

The net result of these two ways is than when a signal arrives along the upstream axon, more neurotransmitter molecules are released at once, and they have more available reception sites waiting for them, so stimulation potential builds up on the dendrite side easier/quicker, and the downstream neuron will fire more readily.

Now, all this intricate bio-chemical process is referred to as “rewiring” (or “wiring”)!… Do you see what I mean? Not very helpful. When I think about rewiring my DIY electronic rig, I typically think about switching on my soldering iron and looking for the tin wire, about stripping insulation, twisting copper strands together, about looking for some heat-shrink and about how to ensure substrate continuity and mechanical strength. Quite different.

I do also understand that in the earlier days of neuroscience it might have been useful. Back when not much was known about the intricate workings in synaptic gaps, and how upstream and downstream neurons adjust dynamically over time, both influencing and being influenced by everything going on in those gaps (and possibly elsewhere in the system). But perhaps it’s time to adjust our terminology, and maybe act as more responsible popular-science ambassadors (self-appointed, haha). We can use “bonding”, “co-adjusting”, “attuning”, “affiliating”, and so on (and maybe also use “re-” where it makes sense).

Before I end this post, I want to mention that there is a specific case in which “rewiring” makes a little more sense to me. Science tells us that when a neuron dies (or is dying), the axon of an upstream neuron which was/is connected with it might “grow sideways” and connect with the dendrite(s) of another neighboring neuron. “Rewiring” feels like a useful metaphor in this case, though in line with everything I argued above I’d prefer “reconnecting”.

Either way – peace to all. See you next time.

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Did you know…? There are more posts in this blog than are presented to you right now. It’s an attribute of the template which I can’t change.
How to see all of them?
Click on the header – the bold “The Meaning of Life and Other Vegetables” at the top. You’ll get a list (which is not complete either), with a button at the bottom to access the next list, and so on. Those go all the way back to my first post in this blog.
Enjoy Reading!