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.