1963 Nobel Prize in Physiology or Medicine — Eccles, Hodgkin, and Huxley: How Do Neurons Transmit Excitation?

What You Will Learn in This Article

You will understand how the two hypotheses that had been in conflict until the early 20th century (is neural excitation like electricity flowing through a wire, or is it the movement of chemical substances?) were integrated into a hybrid solution through the research of three individuals; what Hodgkin and Huxley measured in the giant axon of the squid; how Eccles discovered the inhibitory postsynaptic potential (IPSP) in the synapse; and how these discoveries became the foundation for the treatment of neurological diseases and the basic science of the brain today.

A Story Different from Common Knowledge — Is a Neuron a Wire or a Pipe?

The common sense notion that "neurons transmit signals" was in a very ambiguous state until the mid-20th century. Two hypotheses stood side by side. One held that neuronal excitation was an electrical conduction phenomenon, like electricity flowing through a wire; the other held that a chemical substance moving across the cell membrane between the cytoplasm and the outside carried the reaction. Neither hypothesis had decisive experimental support, and both coexisted uneasily for a long time. Only one thing was commonly accepted — that a potential difference exists between the inside and outside of neurons.

The ending is that both hypotheses were partially correct. Neurons are a hybrid system — signals are transmitted electrically (more precisely, by the movement of ions) within the axon, and signals are transmitted chemically (neurotransmitters) at the point where they meet other neurons (the synapse). The reason for the intense debate in the early 20th century was that only partial measurements were possible, and the research of the three laureates combined these parts.

In the language of computer science, the signal transmission of a neuron is a hybrid protocol of an event bus and RPC. The inside of the axon is like an event bus, propagating low-latency electrical signals, while the synapse is like RPC, with emission-reception-processing tailored to specific protocols (types and amounts of neurotransmitters and receptors). The decisive implication of this discovery was why this hybrid was necessary.

The Landscape of the Time — A Year of Disappearing and Emerging Leaders

1963 was a year when the political landscape was shaken in many places.

In world history, the assassination of President Kennedy on November 22nd occurred. This event, which took place during a motorcade in Dallas, Texas, fundamentally changed American politics and remains one of the most frequently mentioned events in 20th-century American history. In August, Martin Luther King Jr.'s March on Washington and his "I Have a Dream" speech took place, and in the United Kingdom, the Profumo affair, which involved the Secretary of State for War, shook the government.

In Korean history, Park Chung-hee took office as President on December 17th. After two and a half years of military rule following the May 16th coup, he was elected in a presidential election that was conducted in the form of a transfer of power to civilian rule. This marked the official beginning of the 18-year Park Chung-hee era.

In this year, the Nobel Committee recognized the mechanism of neural excitation conduction. In a year when the decisions of leaders rapidly changed the political landscape of the continent, the mechanism by which excitation is transmitted from one neuron to the next was revealed — a year in which the signal transmission of politics and the signal transmission of the body were observed together.

The Three Laureates — Cambridge and Australia

John C. Eccles (1903-1997) was an Australian physiologist. He received his Ph.D. from the University of Melbourne (1929) and was a professor at the Australian National University (1951-1966), and in his later years, at the State University of New York (1968-1975). The problem he had been grasping since early in his career was this — how does excitation traverse the narrow gap between sensory cells and neurons, and between one neuron and the next? This single question ultimately guided him toward the mechanism of synaptic transmission.

Alan L. Hodgkin (1914-1998) was a British biophysicist who graduated from Cambridge University (1936) and was a researcher at the Cambridge University Physiology Laboratory (1952-1969) and a professor at Cambridge University (1970-1981).

Andrew F. Huxley (1917-) was a British physiologist. He earned his master's degree from Cambridge University (1940) and was a lecturer and professor at Cambridge University (1941-1960), and later a professor at the University of London. He was also known as a descendant of the famous evolutionary biologist Thomas Huxley.

Hodgkin and Huxley were longtime collaborators at Cambridge. They elucidated the physics of electrical conduction within the axon, while Eccles elucidated the chemistry of synaptic transmission.

Hodgkin and Huxley — Ion Channels in the Squid Axon

The subjects of Hodgkin and Huxley's measurements were the giant axons of squid. This axon is about 1 mm in diameter, which is 100-1000 times thicker than a human axon (1-10 μm), making it the only material that allowed them to directly measure the potential inside and outside the cell by inserting microelectrodes. It was an experimental material that nature had given them.

Their decisive experiment was the voltage clamp technique. This is a method of inserting electrodes inside and outside the axon to forcibly fix the cell membrane potential at a desired value and then measuring the ionic current that flows. With this technique, they elucidated the physical reality of the action potential.

The way ions flow creates the action potential is as follows:

• Resting state: A potential difference of about -70 mV exists between the inside and outside of the cell membrane. The inside is negative and the outside is positive. K+ ions are abundant inside the cell, and Na+ ions are abundant outside the cell.
• Stimulus arrival: When a stimulus arrives at a specific point on the cell membrane, the potential difference begins to decrease (depolarization).
• Threshold reached: When a specific threshold (about -55 mV) is exceeded, the Na+ channels open explosively, causing Na+ ions to rush into the cell and the potential to rapidly reverse to +30 mV.
• Repolarization: The Na+ channels close and the K+ channels open, causing K+ ions to flow out of the cell and the potential to return to -70 mV.
• Wave propagation: This local potential change raises the potential at the adjacent point on the cell membrane above the threshold, causing the same explosive reaction to occur at the next point. The action potential travels along the axon like a wave.

This understanding is summarized in the Hodgkin-Huxley equation (1952). This model, which expresses the relationship between cell membrane potential and ionic current with four differential equations, is still used today as the standard model for neural simulation. It is the true starting point of computational neuroscience.

Eccles — Inhibition in the Synapse

While Hodgkin and Huxley were elucidating electrical conduction within the axon, Eccles explored what was happening in the synapse. His decisive finding was this: when inhibitory chemical neurotransmitters are released from the axon terminal into the synapse, the terminal of the receiving postsynaptic neuron is pushed into a hyperpolarized state, making it harder to excite. Eccles named this phenomenon the inhibitory postsynaptic potential (IPSP).

The significance of this discovery is as follows: Until then, the synapse was understood only as a place that transmits excitation to the next neuron. By showing that there are also chemical neurotransmitters that inhibit excitation in the synapse, Eccles demonstrated that the synapse is not a unidirectional activator but a bidirectional regulator.

Why is this discovery so important? Because it provides the physical basis for how the brain makes complex decisions. If there were only excitatory synapses (EPSPs), the brain would be limited to a simple switch circuit. It is the existence of inhibitory synapses (IPSPs) that makes it possible to sum and selectively activate multiple signals. The system in which each neuron determines whether or not to fire by receiving excitatory and inhibitory signals from hundreds or thousands of synapses is what we understand today as the prototype of a neural network.

Eccles has one more important experience. He was originally the leader of a school of thought that claimed that synaptic transmission was electrical. After conducting his own measurements and discovering that the synapse was chemical, he publicly retracted his previous claim. This is a frequently cited example of a scientist who abandoned his own theory in the face of empirical evidence.

Compressed into a single line, the finding reads like this. Eccles used direct measurement to reveal the process by which excitation (the action potential) is transmitted or blocked (inhibited) at the synapse — the meeting point between one neuron's axon terminal and another's dendrite terminal. This finding, for the first time, provided a physical basis for the phenomenon by which excitation travels from the periphery to the central nervous system and back out again, coordinating the animal's behavior.

Event Bus vs. RPC — A CS Framework

Now let's summarize the discoveries of the three people in the language of computer science.

An Event Bus is a communication protocol in which various components within a system publish and subscribe to events. The publisher throws an event onto the bus, and the subscribers each receive and process it. Its advantages are low latency, high bandwidth, and a simple structure, but it is difficult to negotiate the details of the types of events.

RPC (Remote Procedure Call) is a method of defining a specific function signature and protocol and performing a remote call. Its advantages are detailed parameter and type stability, but each call has a high overhead.

A neuron is a hybrid of the two:

• Inside the axon is an event bus: The action potential travels along the axon. It is not a specific information but a simple event that "the threshold has been exceeded." There is no protocol negotiation, it is low latency, and it is fast. This is the part that Hodgkin and Huxley measured physically as accurate electrical propagation.
• The synapse is RPC: Specific neurotransmitters are released from the axon terminal to a specific receptor. Each synapse has its own protocol (which substance, which receptor, excitation/inhibition). The inhibitory synapse (IPSP) that Eccles demonstrated is one of the specific RPC function signatures.

Why is this hybrid necessary? If everything were electrical, it would be difficult to express the diversity of which neurons are connected to which neurons, and if everything were chemical, the signal transmission would be too slow. Long distances are electrical, and short distances (synapses) are chemical — this division is the optimization that nature discovered through evolution.

Limitations of the analogy: Of course, the signal of a neuron is much more probabilistic and state-dependent than a computer protocol. The same stimulus does not always produce the same firing, and the spatiotemporal summation of multiple synapses determines the decision. However, the fundamental design of "long distances are events, and short distances are protocol negotiations" is remarkably consistent.

The Legacy Continues

The scale of the door opened by these three researchers' work on nerve impulse conduction can be captured this way. From that point on, neurophysiology built on their results to fully unpack the molecular mechanisms of action potential conduction within neurons, transmission at synapses, and excitation transfer between muscle cells and neurons. A whole family of neurotransmitters — starting with acetylcholine — was discovered, and their individual actions were mapped, explosively enriching the foundational data of brain function research. Beyond neurophysiology, the impact reached deep into clinical medicine and the treatment of neurological disorders — and the starting point of all of it traces back to these three men.

This flow leads to the following applications we see today:

• Treatment of Parkinson's disease: It has been discovered that the deficiency of dopamine, a neurotransmitter, is the cause, and treatment is achieved through the administration of L-DOPA. A representative example of understanding the system based on neurotransmitters.
• Antidepressant and antipsychotic drugs: Drugs that regulate the reuptake of serotonin, dopamine, etc. (such as SSRIs) have been developed. Understanding the chemical transmission at synapses provides drug targets.
• Treatment of epilepsy: With the understanding that runaway action potentials are the cause, various drugs that regulate ion channels have been developed.
• Local anesthesia: Lidocaine, which blocks Na+ channels, locally blocks the propagation of action potentials, preventing pain signals from reaching the brain.
• Artificial neural networks (deep learning): The structure in which each unit activates after summing the weighted inputs and exceeding a threshold is derived from the model of EPSP/IPSP integration in neurons. One of the core principles of artificial intelligence today.

Why is it important?

What these three individuals left behind is a fundamental example of the principle that "a complex system can be composed of a hybrid of simple principles."

At the time, scholars debated whether nerve impulse transmission was electrical or chemical. These three individuals resolved this dichotomy by stating that both are correct and operate in different locations. Electrical in the axon, chemical in the synapse. This separation is not accidental but rather the physical optimization of information transmission, as later revealed.

This principle is still used as a guideline for system architecture today. Do not try to solve all problems with a single communication method; instead, combine multiple methods that are appropriate for the situation. This is exactly the approach taken when microservices use gRPC for internal communication, Kafka for event processing, and Redis protocol for caching.

Another, more profound implication is "the courage to abandon one's own theory in the face of empirical evidence." The case of Eccles, who discarded his own theory of electrical synapses based on his own empirical results, remains a model in the history of science. A good scientist respects empirical evidence more than he loves his own theory.

1963, Eccles, Hodgkin, and Huxley Summary: Hodgkin and Huxley elucidated the ionic channel mechanisms of action potentials in squid giant axons using voltage clamping and quantified them with the Hodgkin-Huxley equation (1952). Eccles discovered inhibitory postsynaptic potentials (IPSPs) in the synapse, demonstrating that the synapse is not only an excitatory but also an inhibitory regulator. This forms the theoretical basis for the treatment of neurological diseases and artificial neural networks.

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