Imagine that you want to build a house. You need to know how all the different parts of the house are connected together in order to build it correctly. Connectomics is like the blueprint for the house. It tells you how all the different parts of the brain are connected together, and how these connections work together to control our behavior. It's like a map of all the roads in a city, but instead of roads, it's neurons and synapses.

Neurons are the cells that make up the brain, and synapses are the connections between neurons. Connectomics helps us to understand how these connections work together to control our behavior. For example, if you want to learn how to ride a bike, you need to learn how to coordinate your muscles and your senses. Connectomics can help us to understand how the brain learns to do this by mapping the connections between the different parts of the brain that are involved in riding a bike.

Connectomics is still a new field, but it has the potential to revolutionize our understanding of the brain and behavior. As we learn more about how the brain works, we can develop new treatments for neurological disorders and create new technologies that can help us to improve our lives.

My current wheelhouse is the fruit fly, also known as Drosophila melanogaster. Yes–I study the bug that keeps showing up after you’ve purchased bananas. Ever since all these connectomic papers came out, the most common questions I’ve been asked so far when explaining my and my lab’s research are,

These questions aren’t naive at all to ask–at face value there's no obvious reason to study the fly to this depth for the betterment of society. To map every neuron and synapse and its influence on other neurons and synapses in a bug is giving “waste my time” energy to the majority of the US populus at least. For a while I sorta agreed with this, but as I’ve been progressing through this hellscape known as a Ph.D. my stance has shifted.

You’d be surprised to know that A. we are human, and B. as a society we care a lot about…well…us mostly. As scientists we do a lot to figure out what the hells going on in our bodies and our tax dollars pay for it. We focus on rodent models and other vertebrate species to facilitate the discovery of new genes and new concepts about the brain to understand how we do what we do, and what's happening when things go awry. So how does the fruit fly fit in this? How would a bug help in this discovery and advancement of us?

In short, the fruit fly has like less than ~200k neurons in its entire body, compared to approximately 100 billion neurons MAYBE in humans.

Is your mind blown yet? Should be at this point…

The fly's nervous system is very similar to the human nervous system, but it is much smaller and easier to study. This alone is a ‘yuge reason why the fly can help us.

Another reason: motor behavior. Motor behavior is how an animal moves its body. For example, how a fruit fly walks, flies, or eats. By studying the wiring diagram of the fruit fly’s nervous system, its connectome, scientists can learn more about how the human brain controls motor behavior. This is important because it can help us to understand how motor behavior works, because we still don’t completely know..

For example, if scientists can understand how the fruit fly brain controls walking, they can learn more about how the human brain controls walking. Let's imagine that you want to build a robot that can walk. You could start by studying how a human walks. But this would be very difficult, because the human brain is very complex, behavior is variable, and you have no context as to what's REALLY going on in that pink goop upstairs (your brain). A better way to do it would be to study how a fruit fly walks. By our lab studying proprioception, the sense that tells you where your body is in space, in the fly, we can better develop new treatments for neurological disorders that affect motor behavior, such as Parkinson's disease and Alzheimer's disease. There's your human health relevance.

Drosophila connectomics offers us what we can’t achieve yet in humans: a window into the pink goop. Our lab and others around the world are using connectomics to study motor behaviors in flies, and they’ve made quite the stride in mapping the neural connections in the adult fruit fly nervous system.

We now have three connectomes for the fly–a female and male nerve cord, similar to our spinal cord, connectome, and a whole fly brain one–all of which contain a high-resolution map of the fly’s wiring system. We recently found out several new neural circuits that are involved in important behaviors, such as locomotion, flight, grooming, olfaction, vision, and navigation.

The fruit fly brain itself is much more modular than previously thought; each connectome is organized into several modules, or blocks, each of which is responsible for a specific function for the fly. For example, one module is responsible for locomotion, controlling the relationship between two or more muscle groups to coordinate walking in the fly, while another module is responsible for flight production, how the beats of a fly wing are controlled to execute flying and potential escape. The connectome also reveals a number of long-range connections between different modules. These connections are important for coordinating the activity of different parts of the nervous system. And spoiler alert: we have a very similar organization in our nervous system, too.

figure from Azevedo and Lesser, 2023

The future of connectomics is bright. As the field continues to advance, we will learn more about how the brain works and how to treat neurological disorders. We will also be able to create new brain-computer interfaces that allow people with disabilities to control devices with their thoughts.

But it has its challenges, like literally everything else on this planet. We’re far from a human brain connectome. The human brain is more complicated than your relationship with your ex, and the connections within it aren’t static. They change over time, in response to experience and learning, like how you’ve learned so much from your ex. This makes it just generally difficult to map the connectome of a living brain. On top of that, it's also not likely that the human brain will somehow decrease its number of neurons in it to make it simpler for us (some of us clearly already have less, like Trump or the SCOTUS, and we’re praying for them I guess).

But..despite these challenges, the field of connectomics is making rapid progress. New technologies are being developed that make it possible to map the connectomes of larger and more complex brains, like mice.

Connectomics is a powerful tool that has the potential to transform our understanding of the brain and to improve the lives of millions of people.

For me, I am excited to see what the future holds for this field, whether I’m in it at the end or not. Something is oddly satisfying about trying to know what makes a fly tick (or..fly), and delving deeper into neurons and synapses and chemicals and all that…debugging a bug.

Here a *very short list for deeper (more science-y) reading on connectomics and its applications in the fly:

1. Tools for comprehensive reconstruction and analysis of Drosophila motor circuits

2. Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy

3. Systematic annotation of a complete adult male Drosophila nerve cord connectome reveals principles of functional organisation

4. Neuronal wiring diagram of an adult brain