More Separate Than We Know

MORE SEPARATE THAN WE KNOW

Other Dimensions of Our Distance

Time is the longest distance between two places.

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SO THERE we have it. Within our physical systems, we have built-in distance, unavoidable separation between the world which keeps us from actually contacting anything (or anyone) up-close-and-personal. The length of our neurons – some of them as long as 3 feet – which send electrochemical sensory information from sense origin to brain, and back again, creates a “buffer” between us and our surroundings. And synaptic clefts, numbering in the trillions, create even more separation between ourselves and what we sense. No matter how minuscule those individuals gaps may be, their aggregate distance is still measurable – to the tune of hundreds of millions of miles. And that’s not even counting the round-trip distances that all the biochemical neurotransmitters cover, shuttling between their vesicles of origin, receptors, neighboring astrocytes, and back whence they came.

It all adds up.

But the physical aspects of our innate separation are really just the tip of this metaphorical iceberg. In many other areas of our lives, we are distanced, as well. That can be deliberate, or unintentional. By chance or by design or by force. Whatever the reason, whatever the source, distance is indeed a hallmark of human experience.

We may try to dismiss the idea of widespread separation. We may tell ourselves it doesn’t matter. Yet, it’s so central to who we are and how we function, we don’t even realize the extent to which it permeates our day-to-day lives. Distance is useful. In some situations, it’s even essential. And in fact, we actually create separation, so we can use it in our favor.

Let’s take a closer look at how that happens and what we do with it.

So What?

So What?

Now the point of this discussion is not to definitively express the total distance covered by all that electrochemical activity in our systems in numbers with so many zeros we need scientific notation. I’ve used approximate numbers on purpose. I just want to give you a tangible sense of the actual magnitude of the distance which exists within our nervous systems. Separation is not a figment of our imaginations. Distance is not foreign to us. It’s not a sign of abnormality. On the contrary, it’s all built into our systems at the most fundamental, cellular level.

If you’re put off by this idea, you’re not alone. Camillo Golgi, the Italian Nobel Prize winner for Science in 1906 – who enabled scientists to get a look at actual neurons through his staining technique – flatly denied that neurons could be separate. He insisted that, like the vascular system, nerves were continuously connected in a diffuse network. He shared the Nobel Prize that year with Spanish neuroanatomist Santiago Ramon y Cajal, who along with others insisted (without actually being able to see) that neurons had to be separate.

History (and the electron microscope) eventually proved Ramon y Cajal and other adherents to the “neuron doctrine” correct. But it doesn’t change the fact that for most people (who don’t really know or care about neuroanatomy), the idea of all that separation within our systems can be deeply unsettling. Many of us rely on a sense of undifferentiated connectedness to feel secure in our world. We turn to direct contact, immediate perception for our most reliable sense of security. We trust what’s up close and personal, and we shy away from people and ideas that feel foreign. But the simple fact is, our very wiring is full of gaps which guarantee we’ll never directly contact anything. Distance, not undifferentiated contact, is a hallmark of our central nervous system. What do we do, in the face of evidence that says true connectedness can never exist?

I myself would love to believe that Unity is possible. I’d love to be sure that we can all truly connect with others and the world around us. I’m tired of all the separation, the divisiveness, the fragmentation of the world around me. But now it appears that fragmentation is the rule, rather than the exception. If we’re really and truly separate from each other on the microscopic cellular level, how can we ever hope to overcome our broader separations that are driving us farther apart, with each passing day? Surely, there must be some truth to the sage declarations that separation is illusion… and that division – Othering – is a product of our politics and choices, not our innate state.

But… science. It’s wrecking everything.

We’ve seen how the measurable separations of those trillions of synaptic clefts rules out direct contact with the world around us. It’s literally never actually possible. As much as we may crave closeness, as much as we may espouse unity and claim that separation is an illusion, we simply cannot argue with the objective fact of the built-in divisions that permeate our physical vehicles in numbers too large for many of us to count. As much as we may want to trust our senses, to rely on them for grounding us in the world… as much as we may believe only our own immediate experience of life… that doesn’t change the fact that the neurological highways that connect us to the world are riddled with gaps that cannot – by definition – be directly connected.

Separation isn’t the illusion. Unity is.

How Can That Be? We’re Supposed To Believe That Thousands Of Miles Are Covered Each Day Just Within Our Brain?

How can that be? We’re supposed to believe that thousands, even millions, of miles are covered each day just within our brain? It’s impossible for all that distance to be traveled in such a small space. Isn’t it?

Again, it seems counter-intuitive, but consider that linear space isn’t the same as 3D space. Synapses can share cleft space with additional glial cells (the “glue” between the neurons which serve a number of functions and hold them in place). Myriad neurotransmitters will not only traverse that shared space to get from their originating vesicles to their appropriate receptors, but also get taken up by astrocytes or diffused into the space around the neurons. Even though the actual gap between dendrites and axons may be ~20 nm, the distance traveled by each individual neurotransmitter can be longer.

So, a 20 nm space, crossed just once by 2,000 neurotransmitters, and then again by 500 of them on the return trip to uptake will involve cumulative linear travel of 50,000 nm, or .005 centimeters, or a little less than 2/100th of an inch. And that’s the math for just one synaptic vesicle (out of hundreds), on just one neuronal synapse (of billions), each of them firing around 200 times/second to release neurotransmitters.

Here’s a (rough and simple) visual approximation of that “travel”:

 20 nm synaptic cleft x 2000 neurotransmitter "trips" 
  • 20 nm synaptic cleft x 500 neurotransmitter “return trips”

x 200 releases per second

= ~10 million nm crossed => .3937 inches per synapse

That’s a lot of travel. Especially for minuscule entities of .5 nm in size. And that’s not even counting all the activity in the spinal column, which has its own many millions of chemical neuronal connections. When you consider the constant movement and flow of neurotransmitters involved in even the simplest activities, which multiplies the totals even more, my math completely fails me. It all adds up to a number that’s better quantified by a computer. Or a savant.

Each tiny neurotransmitter is a fraction of the size of the synaptic cleft

Each tiny neurotransmitter is a fraction of the size of the synaptic cleft, ranging from .5 to 5 nm so the distance from axon to dendrite can be anywhere from 4 to 80 times the size of that tiny chemical. Each vesicle can contain 1500-2000 neurotransmitters each, which (roughly) adds up to a potential 300,000-1,000,000 microscopic travelers across each 30 nm space.

Let’s do the math on a modest estimate of 300,000 individual neurotransmitters traveling less than half the available distance in the brain. That assumes some activity, not being 100% switched ON.

1000    miles of travel distance inside the brain

x 300,000   trips made by neurotransmitters

= 300,000,000   cumulative miles 

That’s 300 million miles of cumulative distance those neurotransmitters will travel within the brain, conservatively speaking.

Now, consider also that each of those neurotransmitters may not cross the synaptic cleft in a straight line. The actual distance involved may be even more. For the sake of this discussion, 30 nm is the average space between, but the neurotransmitters may angle (or wander) across the cleft, adding a minuscule but cumulative amount of distance involved.

What’s more, neurotransmitters may not even stay within the synaptic cleft. They can also be released into the space around, binding to other supporting cells (astrocytes, for example) near the neurons, which may be farther than 40 nm away from the vesicles of origin. Some astrocytes can be as far from the pre-synaptic membrane as 1 µm (1 micrometer, or 1000 nm).

So, the actual distance involved in all those trillions of neurotransmitters crossing the synaptic cleft may be considerably more than 300 million miles.

But this distance doesn’t even account for “round trips” by a percentage of the neurotransmitters, which return to their originating axons for a process called “reuptake”. Neurotransmitters which haven’t bound to a receptor on the other side of the synapse are sucked back across the synaptic cleft and re-absorbed into the vesicles. Some drugs, such as SSRIs, act to inhibit that process. If you don’t inhibit reuptake, however, the neurotransmitters which haven’t bound to the receptors on the far side of the cleft can get recycled by the axon that released them. And that return trip increases the cumulative distance traveled even more.

But the biggest numbers show up, when we consider how many times synaptic clefts are getting crossed – and re-crossed – by those millions of neurotransmitters during our every living moment. Electrical impulses stimulating the release of neurotransmitters – as often as 200 times per second – are the hallmark of life. They pass along vital information about our environment and allow us to respond appropriately. We’d literally be dead without them. And a mind-boggling number of trips are being made on a moment-by-moment basis, which we can hardly even begin to conceptualize without substantial computing power.

The human brain is approximately 1130-1260 cubic cm in volume

The human brain is approximately 1130-1260 cubic cm in volume. Since 1.13 septillion (1,130,000,000,000,000,000,000,000) nanometers will fit into a 1130 cubic cm space, we actually have plenty of space for those paltry 4500 trillion nanometers – especially because they are scattered throughout the space, in a dithering of chemical potential.

Now, when we add a third dimension, things look even more feasible. According to Alonso-Nanclares, et al, every cubic millimeter (mm) of cerebral cortex contains roughly a billion synapses. So, 150 trillion synapses takes up 150 cubic cm. In terms of volume, that’s about 3.5 cm x 3.5 cm x 12 cm – about the size of a stick of butter.

So, that’s not so massive, considering it’s spread throughout the 1130-1260 cubic cm of the brain. And yet, that’s enough room for 150 trillion synapses, shared by 86 billion neurons. In the brain alone.

When you think about it, it’s pretty amazing just how much is folded into that relatively small space. Our bodies are highly adept at embedding length into compact spaces. The small intestine, which shares space in our abdomens with other internal organs, measures some 23 feet (7 meters) when you stretch it out. And the DNA in a single human cell totals about 6 feet (2 meters) in length. This all works because of 3D space, as well as the incredibly tiny dimensions of the elements in question. So, our nerves and synapses are simply following suit, fitting a whole lot of functionality and information in a compact container.

But let’s get back to linear distance. Remember the illustrations of the synapse earlier? At the end of each axon, we find a “bouton”, or a terminal, which is the pre-synaptic “start” of the synapse. Nerve terminals in certain parts of the brain typically contain approximately 200-500 synaptic vesicles per terminal. Those vesicles are the “pockets” at the ends of the axons holding the biochemicals which travel across the synaptic cleft.

The scope of this system is pretty amazing

The scope of this system is pretty amazing, if you think about it.

Let’s consider the brain (only the brain – no spinal column or other neuronal networks) of an average adult male. It contains an estimated 100-500 trillion synapses (let’s use a conservative 150 trillion for this discussion). That’s 150 trillion possible connections between axons and dendrites in the brain itself. Just to give you a sense of the scale, if you had a dollar for each of your synapses, you could personally pay off the U.S. Federal debt 7 times over.

Now, as we mentioned earlier, each synapse includes a synaptic cleft, which is estimated 20-40 nanometers (nm) in width. 1 nm = one 1-billionth of a meter. A sheet of paper is ~100,000 nm thick, and a human hair is approximately 80,000 – 100,000 nm wide.

Let’s average the synapse width to 30 nm.

150 trillion synapses at 30 nm each = 4500 trillion nanometers.

Which, in terms of everyday distance converts to

4500 kilometers, or nearly 2800 miles

That’s the driving distance between Toronto and Vancouver, all dithered across trillions of synapses in one human brain alone.

But that can’t possibly be… can it? How could that much space fit inside the human brain? Well, if you consider that the span of a synapse is ~30 nm, you have plenty of room, especially if you double it back on itself.

3800 pixels will fit into a 200-pixel-high space, when folded back on themselves

A Broken Chain With No Missing Links

A Broken Chain with No Missing Links

Perhaps one of the most amazing thing about this process is that all the communication doesn’t take place in a single “stream” of signals between the sensed world and our systems. Our nerve cells are in contact with each other, but they’re not all continuous. Some neurons are long enough to transmit a signal from the point of sensation to the spinal cord (neurons that go from the toe to the spinal cord can be up to three feet long). But billions of neurons are much shorter; some are only a fraction of an inch. To do their part, they pass their information over “synapses” (gaps between the axons and dendrites of separate but connected neurons).

The term “synapse” comes from the Greek synapsis which means “conjunction” or something that “fastens together”. Somewhat contrary to the idea of fastening, synapses don’t always firmly attach axons and dendrites. In the case of electrical synapses, tiny protein “gap junctions” do connect axons and dendrites to pass information at dizzying speeds. But with chemical synapses (the vast majority of synapses in our bodies), there is always a minuscule gap, a distinct and unavoidable separation between neuronal transmitters and receivers.

So what does connect those separated nerve cells? It’s not a physical bridge (like the gap junctions mentioned above). Rather, it’s a biochemical process that’s part of each and every chemical synapse. Biochemical neurotransmitters are released from “synaptic vesicles” at the “button” ends of axons and travel across the synaptic cleft to dendrites which have receptors specific to those particular chemicals. Once they reach the post-synaptic dendrite, those neurotransmitters stimulate more impulses which continue the lightning-fast relay of sense information to the spinal column and brain.

The brain/body then decodes it and decides how to respond to it. And the resulting reaction – a quick stop before striking a pedestrian, a step back from a wet field, or a dash to the shelter of the car – completes the loop.

Each neuron may have thousands of synapses, and with billions of neurons in the human body (an estimated 86 billion of them in the brain alone), it’s commonly estimated that we have an average of 150 trillion synapses – each with its own tiny gap. Not every single synapse is constantly activated, of course. Our systems might short out if that happened. But cumulatively speaking, that’s a lot of gaps built into our systems. Even if you conservatively count the active clefts in terms of thousands (or millions), that’s a considerable cumulative distance for all the information to travel.