Scientists have been studying the brain and nervous system for hundreds of years.
Nowadays, scientists have all kinds of fancy tricks and tools to study how the brain works
- we’ve got optogenetics and green glowing mice and we’ve even mapped out every single
synapse in the C. elegans nervous system.
But those inventions are pretty new.
So what did the neuroscientists of yesteryear use instead?
Our ink-redible cephalopod friends!
Yep, as wild as it sounds, scientists have actually learned a lot from....squid.
And more specifically, the giant squid axon.
Now, just to clarify - I mean the giant...squid axon, not the giant squid...axon.
We’re not talking about the kraken here.
Nope, just the humble, ordinary squid.
See, back in the mid-1900’s, we didn’t have all those fancy tools to let us study
brain activity.
So scientists had to get creative when it came to figuring out how brains actually...ya
know, work.
At that time, options were pretty limited, because of course, you couldn’t just go
digging around inside people’s heads...although doctors did perform a /lot/ of lobotomies
around that time.
But it wasn’t very precise or...you know.
Evidence-based.
We were still relying on things like lesion studies to help us understand what different
parts of the brain did - and we didn’t fully understand /how/, exactly, neurons send signals.
These days, we know that neurons send electrical signals called action potentials using ionic
currents and pumps to change the electrical potential along the cell surface in the axons
of neurons.
What that means is that the /inside/ of the neuron is “more negative” than the outside
- there are more negative ions bumping around inside, which keeps the voltage at about -70
millivolts.
But when a neuron receives an incoming signal, that ionic balance gets disrupted, and the
voltage inside the cell starts creeping upward.
Once it reaches the tipping point of about -55 millivolts, it sets off a cascade, throwing
open the gated ion channels and causing the electrical potential to spike, thus creating
the action potential.
This spike then travels along the axon, where it can push the axonal terminal to release
chemicals called neurotransmitters, to pass the message on to the next neuron in the chain.
But when neuroscientists Alan Hodgkin and Andrew Huxley were first studying action potentials
in the mid 1900s, they didn’t have the tools necessary to measure these potentials in humans.
Instead, they chose to experiment with the longfin inshore, a small squid.
Now, why in the world did they choose a squid instead of something less...slimy and squishy?
The decision came down to one thing: CALAMARI NIGHTS!
Just kidding.
It’s because of the squid’s giant axon.
Although these creatures are only one to two feet long, the giant axon measures up to 1.5
mm in diameter - which is about the diameter of this pipe cleaner - making it more than
a thousand times wider than typical human axons.
Why would a dinky little squid need such a huge axon?
Well the axon connects to the water jet propulsion system and, in the wild, this allows the squid
to rapidly escape from predators.
*cue squid zooming off screen* Wide axons transmit electrical signals much faster than
thin ones, as the added thickness allows a larger number of electrons to flow through
at any given time.
Humans can get around this limitation because we have myelination around most of our axons,
which act as insulation for the neurons and helps us transmit signals faster.
Instead of myelin, squids just evolved an enormous axon - after all, the faster they
could escape, the more likely they were to survive and be able to pass on that trait
to their offspring.
This wide axon of the longfin inshore squid made them the perfect model organism for studying
action potentials because you could easily insert a wire into the axon in order to measure
the electrical potential.
Back in 1930, a dude named John Zachary Young was studying the nervous systems of sea creatures
- pretty much any species he could get his hands on.
And during his research, he realized that these long, stringy structures that had previously
been mistaken for blood vessels were actually neurons.
He’d discovered the giant squid axon.
A bit later, Hodgkin and Huxley came along and jabbed an electrode in it.
This allowed them to record the first-ever action potential - the spike of a neuron sending
a signal.
To do this, they used technology called a voltage clamp.
When an action potential shoots throughout the axon, sodium and potassium ions flows
in and out of the cell pretty rapidly depending on how the ion channels open and close.
With the voltage clamp, Hodgkin and Huxley could measure how much current they needed
to inject in order to keep the voltage constant while that process was happening.
By doing so, they could track how much charge was flowing into and out of the cell at any
given time.
With this experimental strategy they were able to see that the neuron first experiences
depolarization - that spike that I talked about earlier - and then hyperpolarization,
where it actually overshoots the normal resting potential of -70 millivolts, dipping even
lower down, and creating a barrier that makes it just a little bit harder for the neuron
to send another action potential and helping keep signals distinct.
*insert membrane potential graph?*
But even though they could now see the shape of the action potential, they didn’t actually
know /how/ the action potential was being formed - that is, /which/ ions were going
/where/ to create that quintessential spike.
And obviously you can’t just /see/ ions...so testing it proved to be kind of a challenge.
But Hodgkin and Huxley had another tool in their back pocket.
They added chemicals called tetrodotoxin and tetraethylammonium to the solution they were
keeping the squid axons in.
These compounds block sodium and potassium channels, respectively.
Fun fact: tetrodotoxin is the toxic compound produced by pufferfish and other poisonous
sea creatures that makes them so deadly; it blocks the sodium channels which allow your
nerve cells to send their signals!
By looking at the current when these channels were blocked or when they removed sodium and
potassium from the medium, Hodgkin and Huxley were able to figure out that sodium channels
open first and cause the depolarization phase of the action potential, and that afterwards,
potassium channels open and the outward flow of potassium ions causes hyperpolarization.
This discovery was a huge advance in helping us understand how neurons send action potentials
and how those action potentials could be controlled and manipulated for future experiments.
In fact, it won them the Nobel Prize in Physiology or Medicine in 1963!
Though their choice of model organism may seem a bit strange, Hodgkin and Huxley made
no mistake.
They found the perfect organism for the experiments they wanted to run, with just the right morphology
to help us understand how our own nervous system functions.
Today, squid still play an important role in research, but they aren’t the only sea
creatures being used in neuroscience!
The California Sea Hare is used extensively by neuroscientists studying memory, and the
African Killifish has become an integral part of modern aging research.
So it’s pretty clear that researchers can go beyond mice, worms, and flies when it comes
to choosing animal models for studying the brain!
Big thank you to the International Youth Neuroscience Association for their help researching and
writing the script for this video.
Founded at the 2016 International Brain Bee, the IYNA is an organization of high school
and undergraduate student volunteers who are dedicated to inspiring the next generation
of neuroscientists.
They’re a really cool organization and I highly recommend checking them out if you’re
in high school or early on in college and love this stuff.
To learn more about IYNA and how you can get involved, check out the link down below.
Thanks for watching this episode of Neuro Transmissions!
Until our next transmission, I’m Alie Astrocyte.
Over and out.