What is a connectome?
How do you start your morning?
For me, I wake up, grudgingly make myself a cup of coffee, pet my dog, get changed, pack my bag, and am out the door. This routine and all the senses and memories involved with it — the smell of the coffee, the feel of my dog’s fur, the rush of adrenaline and panic I feel when I realize that I put on two different socks — are all controlled and processed by my brain using billions of electrical connections between nerve cells called synapses.
These cells are interconnected in a vast and very complicated wiring system called a connectome. In its most basic form, connectomics is the study and mapping of the structural and functional connections of individual neurons. Before we get into the larger scale of a connectome, let’s zoom in to the miniature scale at the size of a singular neuron.
Neurons are responsible for receiving sensory input from the outside world. For the nervous system to function, neurons must be able to send signals to each other. These signals are only possible because each neuron has a charged cellular membrane (present in the cell body). A neuron can receive input from other neurons called the axon output which transmits a chemical called a neurotransmitter. If the signal is strong enough ( the threshold reaches — 55mV), the neuron will pass the signal down from the dendrite to the axon terminal.
→ Aaaaannnd repeat. About 100 billion times (and no I’m not exaggerating)
In the picture, we can see a guess of some of these connections. In reality, the connectome is far larger and denser than this. The picture shows an approximation of 100 million neurons; however, humans have over 100 billion neurons with at least 7000 synaptic connections each.
I’m sure you’re asking: “If we know how many connections there are, isn’t drawing out the connectome just a matter of playing a super complicated version of connect the dots?”
Well the answer is yes but also not at all
Brain cells and brain connections are much much different than connections and structures in other organs. Take for example the kidney. The kidney is made up of a million filtering units called the nephron. Once we can understand the structure of the nephron, we understand the Kidney. Because we know its constituent parts we can draw and study and examine the Kidney therefore can create remedies to kidney-related diseases.
Simple right?
The brain doesn’t work like that. In fact, there are more types of cells in the brain than there are in the rest of the body combined. Types of cells. Not the 100 billion neurons we talked about. There is currently research being done on the number of cells in the retina, a tiny tiny piece of tissue near the optic nerve. The number is most certainly going to exceed 50 according to recent research.
That’s just a small piece of tissue. What if we look at the amygdala, or the prefrontal cortex or the cerebellum or the hippocampus. The areas go on and on and the mystery of the types of cells remains a big issue in solving the human connectome.
But I have good news!
We have completed the first complete connectome for an organism. However, this organism just happens to be the amazing, invigorating, incredibly relevant…. C. elegans worm.
I’m kidding, I’m kidding. I am in no way trying to underplay the importance and success of the experiment. The mapping of the connectome of the C. elegans provided incredible insight into the field of connectomics.
There’s just (another) problem)
The way in which scientists mapped the connectome of the C.elegans is not feasible for the human connectome. In order to build its connectome, every neuron was identified, its precise location was determined and every single connection was individually determined. Neural scientists had to follow the path of each individual neuron with their own eyes using endless microscopic images.
Now let’s look at the scale of the C.elegans worm compared to the size of an average human. C.elegans is a one and a half millimetre organism, the size of an average human female is 1600 millimetres (or 5’3). C.elegans has a neural network of 300 neurons and 7000 synaptic connections each so 2.1 million connections total while the average human has about 100 billion neurons with 7000 synaptic connections each so 7 x 10¹⁴ connections total. The structure of the human connectome is roughly 11 times more complex in its connectivity than that of the C. elegans.
Therefore it is impossible for humans to visually and manually create a human connectome.
We currently have a very rudimentary view of the structure of the human brain. If we can understand it and map it, we will be able to cure an innumerable amount of neurological diseases. Think about it this way.
Like before, when we understood the nephron, we were able to explain and create treatments for kidney diseases such as Acetaminophen-induced nephrotoxicity, Acute tubular necrosis, analgesic nephropathy, ciliopathy, preeclampsia, membranous nephropathy and the list goes on and on. We are able to see what’s wrong and understand how to treat the patient based on that knowledge.
With brain disease, the only lead doctors have to go on is descriptors from the patient and neuroimaging which ,down to the neural level, isn’t very helpful. Just imagine how much we could understand with a comprehensive image of the brain. Schizophrenia, Alzheimer’s, dementia, cerebral palsy all these incredibly harmful diseases could have impactful and effective treatments.
Before you get all skeptical, let me remind you, the human genome project, much like the human connectome project, was considered to be impossible, a feat too large to be accomplished. Fast forward to 2020 and guess what? We can edit genes, something that was once considered to be completely dystopian in nature in the past.
Where will the future bring us? The human connectome is still far from being developed but techniques using AI are being currently implemented and with time, hopefully, a full human connectome will be created.
A.N. an article on these AI techniques will be coming soon
