Re-Imaging Neuroscience

Santiago Ramon y Cajal19th century that Spanish neuroanatomist Santiago Ramón y Cajal

Today, most people with a basic science education know what a neuron is. But it was only in the late 19th century that Spanish neuroanatomist Santiago Ramón y Cajal convincingly showed that such cells – rather than an interconnected net of tissue – formed the basis of the nervous system. He used an assortment of anatomical tracing techniques to label neurons in their entirety – a cell body with a long axon extending out in one direction and the branched tendrils of dendrites protruding from the other. In the ensuing decades, researchers explored the electrical and chemical properties that make neurons tick. Australian neurophysiologist John Eccles and his colleagues in 1951 first managed to insert miniscule-tipped probes called microelectrodes directly into a neuron from the central nervous system to measure its responses to signals from neighboring neurons. The following year, based on experiments in the giant squid axon, British biophysicists Alan Hodgkin and Andrew Huxley described how ion flow across the cell membrane generates the electrical spikes – called action potentials – that constitute these signals. Based on those discoveries, researchers turned their attention to investigating the environmental cues or behaviors that make neurons fire. Two neuroscientists working in the U.S. in the 1960s and 1970s, David Hubel and Torsten Wiesel, discovered that in the visual system, different kinds stimuli – a moving line, for example, or a particular color – would turn on certain neurons and not others. Since then, scientists have developed ever-more-sophisticated methods for studying these sensitivities, which are called receptive fields, in individual neurons.

The focus on properties of single neurons was a driving force of neuroscience in the 20th century and remains so even today. But it has proved to be a limited approach. Just as you cannot hear a symphony when only the first violinist plays alone, so the complexities of the brain likely cannot be grasped by examining the functional properties of each individual neuron, measured alone.

More recently, neuroscientists have been able to take a wider view of brain function using new technology to track activity levels across the entire brain instead of individual cells. An approach called functional magnetic resonance imaging (fMRI), for example, records changes in blood flow that occur when a spark of activity passes through a particular brain region. Another technique dubbed magnetoencephalography (MEG) maps magnetic fields in the brain produced by electrical signals; a similar approach, transcranial magnetic stimulation (TMS), selectively stimulates parts of the brain and is already being used to treat severe depression, migraine headaches and other conditions. These newer methods, however, can’t capture the activity of individual neurons, and the picture they provide is therefore too blurry for scientists to directly connect changes in function to distinct thoughts, behaviors, or states of mind. Most importantly, these methods do not reveal the mechanisms by which these elements of cognition occur.