Raising the Voltage
Scientist Walter Rudolf Hess conducted one of the first experiments to test whether neural activity in a defined part of a cat's brain causes specific actions.
In the 1920s, a Swiss scientist named Walter Rudolf Hess conducted one of the first experiments to test the notion that neural activity in particular parts of the brain might cause specific actions. He focused on aggressive behavior in cats, and his work showcased what was then a brand-new technology—electrophysiology, an approach that in some ways foreshadowed optogenetics.
Electrophysiology uses electrodes implanted in the brain to either detect electrical activity or directly activate neurons, which are essentially electrical devices. A neuron normally allows positively and negatively charged ions to flow in and out of the cell, and when the voltage rises past a certain threshold, the neuron fires an electrical pulse. That current races down the axon, which reaches out to other nerve cells and affects their activity. With implanted wire electrodes, electrical current can raise the voltage in nearby neurons so that they fire without the normal signals from other parts of the brain.
In Hess’s cat experiments, he stimulated the hypothalamus to investigate its role in the nervous system’s fight-or-flight response. An electrical surge turned a placid kitty cat into a hissing, spitting beast, while turning off the electrode returned the cat to its docile self. This directly implicated the activity of neurons in the hypothalamus in aggression and the “fight” aspect of the stress response.
In the many decades since then, detecting the brain’s electrical signals and creating new ones have produced remarkable insights about the functions of various brain regions. But it can’t answer many essential questions. What exactly is being stimulated by the electrodes? Which types of neurons are being activated? There’s also the possibility that an electrode in one area of the brain may provoke a response in other regions via long axon fibers.
“Electrophysiology can show correlations between brain activity and a change in behavior,” says neuroscientist Christopher Moore at Brown University. “But it cannot prove that a specific neuron, brain region or circuit causes the behavior.”