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Flinching in response to an unexpected loud noise might not be pleasant, but it's also not a problem for most people. For one family, however, getting startled would cause their bodies to go stiff and fall.

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This episode is sponsored by Wondrium, a subscription service where you find out answers to everything you’ve ever wondered about, and some things you’ve never imagined you would wonder about!

Check out for a free trial. [♪ INTRO]. You might jump or flinch if you hear a loud noise that you’re not expecting.

For most people that’s not a problem. In fact, that reaction comes from one of the basic building blocks of life. But, to figure that out, we had to solve the mystery of “startle syndromes” and why one family reacted very unusually when you bumped into any one of them.

And the fact that it’s different from other kinds of startle response disorders can tell us a little about our own evolutionary history. Startle syndrome, also called hyperekplexia, is a rare disorder in people's reflexive reactions to surprise or agitation. It was first documented in the 1920s.

And in the 50s, doctors described several members of a family who reported unusual falls. A variety of surprises or frights could spark one, but just bumping into them was an especially reliable trigger. Their muscles would go stiff, they'd fall to their knees or to the floor, and after a few moments, they'd get back up again.

Often they'd report being conscious the whole time, and they didn't feel stiff. But still, they became wary about the risk of falling, which, as you might guess, was interfering with their daily lives. So they might avoid things that could trigger a fall, like going up stairs quickly, or even going outside by themselves.

And even though the doctors called the falls "drop seizures," they could tell that this was different from epileptic seizures. Like, it was unusual that they could be so reliably cued by something emotional. Or there was the fact that sometimes they stayed conscious through their fall and tended to get up pretty quickly, both of which are not the case for epileptic seizures.

So doctors were stumped, but at least it was clear that this trait ran in families. When another family was discovered a decade later, they had an opportunity to learn more. Researchers recruited twenty members of the extended family with similar symptoms to be startled in the name of science, all while they were hooked up to an EEG to monitor their brainwaves.

And they found that some brain wave responses were symmetrical across both hemispheres in several different places. That doesn't typically happen. That is to say, in the case of epilepsy, that kind of synchronization happens everywhere, not in specific regions.

So it suggests that the signal was coming from somewhere else that was connected to both hemispheres, so something in the middle, like the brainstem. Several studies tested the reflexes of patients with startle syndrome. Same as when your doctor hits your knee with that little hammer in your knee, though in this case they looked at a muscle in their faces.

Most people flinch automatically, but a reaction in their brainstem helps to tamp it down. But people with startle syndrome had less of that reaction, ergo, more of a flinch. This helped connect their symptoms to a neurotransmitter called glycine, because we have a higher concentration of glycine receptors in the brainstem and spinal cord.

Glycine is one of the brain's primary inhibitory neurotransmitters, meaning the signal it sends makes a neuron less likely to fire. For most people, if you're startled or bumped, you get a reaction of neural activation, and glycine tends to immediately shut it down. And because there are glycine receptors that help signal to opposing muscle groups, it can help you control automatic reflexes from surprises or startles.

That way, a flinching reflex doesn’t make you jerk so hard that your muscles tense up and you fall over. Now, running in families generally means a trait is genetic. And thanks to these folks, we’ve been able to identify the genes related to hyperekplexia.

And all of those genes are related to glycine receptors. They carried mutations in those genes that made it harder for glycine to bind to receptors and send its inhibitory signal. And knowing the specific cause helps to treat it, by targeting a different inhibitory neurotransmitter used throughout the brain, called GABA.

A drug called clonazepam increases the activity of GABA. If your glycine receptors aren’t working right, the drug helps compensate by ramping up GABA instead, another inhibitory neurotransmitter helps make up the difference. Incidentally, Xanax also ramps up GABA, and so does alcohol.

So solving this mystery has been a big help to the families who’ve had these symptoms. But it also connects the story to the origin of complex life. That’s because glycine is one of only twenty amino acids essential to human life, and probably all life as we know it.

These molecules are strung together to make proteins, which carry out most of the functional jobs of being alive. And amino acids all have slightly different chemistries, each suited to slightly different jobs. And glycine is the simplest of them all.

Not something you'd expect to act as a neurotransmitter. But, we've found that some of the simplest organisms on earth use glycine in surprisingly similar ways. Trichoplax is an extremely simple animal that has multiple cells, but no organs and not much in the way of bodily structure.

They’re very old, evolutionarily speaking, and likely resemble some of our first multicellular ancestors. And if you poke these little guys with some glycine, they can shrink down or move, sort of a parallel to motor reflex reactions that glycine supports in humans. In lab experiments, Trichoplax also used glycine as a guide for food sources, moving toward it if it was somewhere to be found in the petri dish.

That means it's possible that these early organisms first adapted sensors for glycine for this basic purpose of finding food. Then, as more complexity developed in organisms and creatures needed a basic way to signal motion in muscle groups, they already had glycine receptors ready to go. And nature has kept on using those receptors all the way up to us.

Now, there are other kinds of unusual startle reactions that don't share this genetic cause. Tourette's syndrome also involves some reflexive reactions that are hard to control, and panic disorder can also involve an extreme response to being startled. But this rare disruption of a tiny molecule’s sensors can show us how we’re connected to some of our oldest evolutionary ancestors, and perhaps all of complex life.

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