Despite the remarkable advances of modern medicine, psychiatric treatments remain stuck at technology from sixty years ago — a consequence of viewing the brain as nothing more than a "soup bowl" of chemicals sloshing around together. In this lecture, Professor Kim Sung-yeon explains the paradigm shift toward understanding the brain as a complex of precision "neural circuits", and how "optogenetics" — a technology that controls specific neurons using light — is leading a revolution in neuroscience. Through this technology, we are entering a new era of discovery in which the secrets of the mind and behavior can finally be unlocked.

1. The Last Frontier of 21st-Century Science: The Brain 🧠

Hello, everyone. I'm Professor Kim Sung-yeon from Seoul National University. Today we're going to take a deep look at neural circuits in the brain and what it means to study them. The brain — especially the human brain — is the central organ that generates our physiology and psychology through 86 billion neurons exchanging countless electrical and chemical signals via 100 trillion synaptic connections.

The brain is often called "the most complex machinery that exists on Earth," and despite more than a century of research, it is still regarded as "the last remaining frontier of 21st-century science." That is why countries around the world — the United States, Europe, Japan, Korea — are investing heavily at the national level.

Neuroscientists study the brain not from a single viewpoint but from multiple levels and scales simultaneously. We look at the whole forest, then the individual trees, and then even the veins of each leaf.

In the past, researchers who studied molecules, circuits, and psychology operated as independently as if they were in separate buildings. But since the 2000s, advances in genetic engineering and optical technologies have demolished those barriers.

We have now entered an era where we can manipulate a single gene to switch a specific brain circuit on — and observe the resulting changes in an animal's mind and behavior all at once.

2. Why Have Psychiatric Drugs Been Stagnant for 60 Years? 💊

Let's take anxiety — one of the central themes of this course — as an example. Anxiety disorders are so common in modern society that roughly 30% of adults will experience one at some point in their lives, and they are deeply linked to other conditions like depression and dementia. Yet remarkably, the treatments we use still rely on benzodiazepines like diazepam (Valium), developed in 1963.

Every year, revolutionary new versions of iPhones and Galaxy phones appear — so why are the drugs we use to treat the brain stuck at 60-year-old technology? (...) Over the past few decades, humanity eradicated smallpox, and treatments for cancer and AIDS have undergone continuous innovation. So why is it that treatments for anxiety disorders alone have not moved forward?

The statistics tell the story clearly: new classes of drugs have poured out for blood pressure and heart disease, while drug development for psychiatric conditions has flatlined. Is it because we don't understand the molecules inside the brain? No. We can map the structure of drug receptors down to the atomic level. The problem lies in how drugs actually act inside the brain.

3. The Brain Is Not a "Soup Bowl" but a "Precision Circuit" 🕸️

Existing drugs like diazepam spread throughout the entire brain and forcibly shut down (inhibit) nearly every neuron. This is essentially treating the brain as a soup bowl in which chemical substances simply float around.

The brain is not only divided into regions by function — within the same neighborhood, the same brain region, neurons with entirely different roles and characteristics are mixed together. It's like the city of Seoul, where students, doctors, police officers, and firefighters all live side by side.

And yet, instead of repairing only the specific circuit that has broken down, we are carpet-bombing the entire brain — which is precisely why side effects like drowsiness and memory impairment are inevitable. Professor David Anderson captured this perfectly with an analogy:

If you need to change the engine oil in your car, common sense says you open the hood and pour the oil into the correct filler cap. But what we are doing when we treat the brain today is the equivalent of opening the hood and dumping the oil all over the engine. If you're lucky, a few drops might reach where they're needed — but most of it will soak the wrong parts and damage the car.

We are now recognizing that "the brain is not a soup bowl but a complex network of networks," and we are taking on the challenge of brain mapping — charting every cell and connection inside the brain.

4. The Technology That Changed Neuroscience: Optogenetics 💡

Having a map is not enough. You have to actually travel those roads and manipulate the traffic signals to understand how they function. That is where the revolutionary technology of optogenetics — controlling neurons with light — enters the picture.

4.1. Background of the Technological Breakthrough

The conventional method of studying the brain — electrical stimulation — indiscriminately excited all cells near an electrode.

Traditional electrical stimulation was not like playing an elegant melody on a piano keyboard. It was like slamming your fist down on the keys. It activated all the cells you didn't want to activate as well.

Scientists dreamed of a tool that could switch only specific types of neurons on or off. The answer came from an unexpected source: Chlamydomonas, a green alga that lives in the ocean. This organism possesses a light-sensitive protein called channelrhodopsin.

4.2. How Optogenetics Works

In 2005, Professor Karl Deisseroth's team at Stanford University successfully transplanted the gene for this algal protein into neurons.

Now, instead of electrodes, we use optical fibers to precisely control neurons with millisecond-level timing — and we can do so by remotely targeting only the specific type of neuron we choose. (...) Science fiction had become reality.

With this technology, it became possible to turn neurons on with blue light (channelrhodopsin) and turn them off with yellow light (halorhodopsin). This allowed neuroscientists to perfectly execute the foundational experimental paradigms of biology — "gain of function" and "loss of function" — at the level of individual brain circuits.

5. The Brain's Secrets Revealed by Light 🐁

Thanks to optogenetics, neuroscience has produced an explosion of discoveries over the past decade or so — just like the videos shown in class.

• Aggression control: When specific neurons in the hypothalamus of a docile mouse were stimulated with light, the mouse suddenly attacked a glove with fierce aggression.
• Thirst and appetite: Stimulating a region called the SFO caused an animal to drink water immediately; stimulating a different region caused it to binge on high-fat food even when already full.
• Reward circuits: Each time a mouse performed a specific action (poking its nose into a hole), the brain's pleasure center was stimulated — causing the mouse to become addicted to that action and repeat it endlessly.

Why exactly was this technology so revolutionary? (...) For the first time in the field of neural circuits, we could causally prove the function of specific types of neurons in brain tissue.

At the center of all this innovation is Professor Karl Deisseroth. Both a psychiatrist and an engineer, he transformed the despair he felt watching patients he could not help into the driving force behind his research. He visited Seoul in 2025 to receive the Asan Medical Prize from Korea.

While doing research, worldly concerns sometimes creep in: "Will this make money? Will this make me famous?" But Nobel laureate Roderick MacKinnon says it plainly: "Just do good science." If you pursue the truth and stay focused on the essence of your questions, recognition and rewards will follow naturally.

6. Closing: New Discoveries Are Made by New Tools 🚀

In recent years, neuroscience has become more technology-driven than almost any other field. Beyond optogenetics, techniques for making brain tissue transparent and imaging technologies for capturing the living brain in action have appeared in rapid succession.

Sydney Brenner, one of the giants of modern biology, put it this way:

"Progress in science depends on new techniques, new discoveries, and new ideas — probably in that order."

When we can finally see what was invisible, and manipulate what was once untouchable, we can at last ask questions that were previously unimaginable. Over the course of this semester, we will journey together through the fascinating story of how these revolutionary tools have unlocked the secrets of the brain. I hope each of you will find a question that makes your heart race. Thank you