For thousands of years, humans have been fascinated with their unique intelligence and computational abilities. The source of this wonderful power has been a mystery since ancient times. Some early humans, recognizing the importance of the brain, drilled holes in the skulls of the diseased (in a process known as “trepanation”). Many, however, denied the significance of the brain and instead attributed homo sapiens’ cognitive dominance to the heart. This was the prevailing paradigm in ancient civilizations such as Egypt: while Egyptians preserved the rest of the body after death, the brain was casually discarded (Bear, Connors, & Paradiso, 2016, p. 4 - 5). The brain’s importance was only truly considered with the dawn of intellectualism and philosophy in Ancient Greece.
Some of the first to attempt to consider the brain’s function were Hippocrates and Aristotle. Hippocrates, known by many as the father of medicine, was the first to posit that the brain is the seat of intelligence and reason. Furthermore, he found that damage to the brain causes paralysis on the opposite side of the injury (Schatz, 2009). This idea is now accepted by neuroscientists, as many (though not all) motor and sensory systems are contralateral, meaning that their axons cross over to the opposite side of the body. Aristotle, a famous philosopher in ancient Greece, had different ideas. He thought that the brain was merely a radiator, cooling blood that goes to the heart. Unfortunately for neuroscience, many people accepted Aristotle’s view, which remained prevalent for over a thousand years in Western thought (Schatz, 2009).
However, not all intellectuals accepted Aristotle’s position. One of the next major researchers to make breakthroughs in neuroscience was Galen. He was the first neuroscientist to study the ventricles, or large fluid-filled spaces inside the brain. He suggested that the ventricles hold pneuma, or animal spirits, that regulate bodily functions such as movement. In addition to this, Galen was a physician to the gladiators. Therefore, he was able to gain specific experience with treating wounded patients (Schatz, 2009). Through this, he learned that some functions were localized to different regions of the brain. For example, Galen correctly surmised that the cerebrum was involved in sensation and memory, while the cerebellum was involved in control of the muscles (Bear et. al, 2016, p. 5 - 6).
Much later, in the 15th century, Descartes discussed his views on the brain. One of his key beliefs was dualism, or a separation between the physical brain and metaphysical mind; however, Like Galen, he accepted the existence of animal spirits, but thought they were physical liquids that flowed through the brain. Therefore, he suggested that the brain followed the same physical rules as other objects. His theories were related to new developments in fluid mechanics (Schatz, 2009). This represents a common phenomenon in neuroscience: the use of modern analogies. Today, we think of the brain as a computer; in the past, people understood it in terms of the technology they had.
With the knowledge that the brain is the primary source of our unique abilities as humans, scientists were now faced with a much more difficult question: How does it work? How does this 3 pound mass of cells control everything that we are? The answer is as complex as the brain itself. The brain is a supercomputer of unimaginable strength, composed of about 80-100 billion neurons. We know this due to the work of Santiago Ramon Y Cajal, widely acknowledged as the father of modern neuroscience. Working together with the Italian scientist Camillo Golgi, they were able to identify the basic structure of the brain as composed of many thin, threadlike structures. However, their opinions differed on the composition of the brain. Golgi believed in the reticular hypothesis, which proposed that the brain was one continuous network composed of many conjoined cells. In contrast, Ramon y Cajal thought that the brain was made of distinct cells, separated by gaps which we now know as synaptic clefts. In time, this theory of independent cells, called neuron doctrine, was proven to be true.
After discovering the structural basis of the brain, scientists concluded that those independent cells had to have some method of communication with each other. One of the first to investigate this was Luigi Galvani, who had already conducted studies on the electrophysiology of movement, or the study of how electricity contributes to normal bodily functions. As we know today, movement is a complex phenomenon in which neurons in the brain send down signals through motor neurons to muscle fibers. Those fibers then contract, in turn moving the desired limb. Galvani discovered that sending an electrical pulse down a frog’s nerve would cause the limb to move, thus disproving Descartes’ fluid-mechanical theory of movement. This was the first in a series of stepping stones leading to the discovery of electricity and it’s use by the nervous system.
Once neuroscientists figured out that neurons communicated through electricity, they began to wonder how they did so. In the 1950s, Alan Hodgkin and Andrew Huxley used voltage clamping, the precursor to modern day Patch-Clamping, to record from individual neurons. This technique uses microscopic recorders to measure the difference in electric potential between the inside and outside of neurons. The pair discovered the output mechanism of neuronal transmission, called the action potential. In action potentials, ion channels in neurons open to allow positive charges to flood into the cell, and another set of channels release these positive charge to restore the neuron’s resting potential, or normal electrical charge. Now, the interesting thing about action potentials is that they work in a binary system—they either fire at full strength, or not at all (Bear et al., 2016, p. 92).
In the early 20th century, there was increasing research devoted to the mechanisms by which messages are transmitted between neurons. Ramon y Cajal’s neuron doctrine suggested that neurons were distinct entities; therefore, posited neuroscientists, there must be some way for the electric charge to be transmitted from the axon, or output end, of one neuron to the dendrite, or the input end, of the receiving neuron. Owing to the presence of the synaptic cleft between neurons, an electric charge is unable to simply pass between two neurons. Thanks to Otto Loewi and Sir Henry Dale, we now know that neurons transmit electrical signals using chemicals called neurotransmitters. Thanks to Dale and his colleagues, acetylcholine was discovered by Dale and his colleagues (in 1914). Later in 1921, Loewi showed its importance in the neurons system. He did so by cutting out two frog hearts, one with the regulatory nerve still attached, and one without the nerve attached. By stimulating the nerve, he found that the heart beat slower. However, when he removed some of the fluid that the first heart was floating in and poured it on the second heart, he found that the second heart beat slower as well. From that, he concluded that there must be some chemical secreted by the neurons that controlled heart rate. Later on, Dale conducted experiments to discover that neurotransmission occurs throughout the nervous system. For their work, Loewi and Dale won the Nobel Prize for Medicine in 1936 (“Neurotransmission Demonstrated”, 2016).
Understanding how neurons communicate was one thing, but to understanding how these microscopic electrochemical changes gave rise to cognitive, motor, and sensory functions represented a major frontier in neuroscience.
In 1809, Franz Joseph Gall suggested that bumps on the skull corresponded to bumps on the brain, and that these bumps corresponded to tendencies towards specific behaviors. Gall called this idea phrenology, and although we now dismiss his claims as pure frivolity, phrenology was a step in the right direction—we now know that the brain does, in many ways, localize function.
Functional specialization gained tremendous credence in 1823, when French physiologist Marie Jean Pierre Flourens used a technique called experimental ablation to prove what Galen had suggested millennia before: that the cerebellum is involved in movement and the cerebrum in sensation. Flourens, however, did not believe that the cerebrum could be functionally subdivided—less because of any sound scientific reason, and more because he was a harsh critic of Gall and could not bring himself to even somewhat accept his views (Bear et. al, 2016, p. 10 - 11).
Functional specialization of the brain would not be solidly accepted until the 1861 discovery by Pierre Paul Broca. Prior to 1861, Broca had seen a patient with an inability to produce speech (even though ability to comprehend speech was largely unaffected). After the patient died, Broca examined the brain and found a localized lesion in the left Frontal lobe of the brain. The implication was that a certain area of the left brain functionally specialized for speech production. Today, we call this area “Broca’s area” (Bear et al., 2016, p. 10).
Elsewhere in the nervous system, neuroscientists were making significant advances in their understanding of functional specialization. In 1810 Charles Bell and Francois Magendie conducted research on the spinal cord. Knowing that nerves attached to the spinal cord form two separate bundles, known as roots, the two aimed to see if there was a functional difference between the two roots. Through experimental ablation (in this case, cutting each root), Bell and Magendie found just that (Bear et. al, 2016, p. 9). The dorsal roots (the root that attaches to the back of the spinal cord) carry sensory information from the body, while the ventral roots (the root that attaches to the front of the spinal cord) carry motor information to the body.
Another functional neuroscientist, Korbinian Brodmann, attained his fame because he “constructed a cytoarchitectural map of the neocortex” (Bear et. al, 2016, p. 210). Brodmann used the physical characteristics of neurons in order to construct a map with the belief that cells that appeared different had different functions. Over the years, his divisions have been proven to be remarkably accurate, with many of the areas he identified corresponding to functional divisions within the brain. Brodmann also studied the evolutionary history of the brain, and proposed that “[the] neocortex expanded by the insertion of new areas” (Bear et. al, 2016, p. 211).
In the early 20th century, Wilder Penfield made an interesting finding regarding the primary somatosensory cortex, or S1 (involved in processing touch sensation). Penfield, when conducting research on surgical patients, noticed that S1 contains different regions that correspond to different parts of the body; the tongue, for example, was found at the base of S1, the toes were found at the top of S1, and the face and hands were found in between. Penfield also noticed that the amount of cortex allotted for each body feature correlates directly with the amount of sensory input from this area (Bear et. al, 2016, p. 431 - 432).
Key Terms (In order of their mention)
Contralateral - Crossing to the opposite side of the body from the brain
Ventricles - four large spaces inside the brain holding cerebrospinal fluid
Dualism - The idea that man has a physical brain, and separate, metaphysical mind
Reticular hypothesis - an outdated theory that the brain is a large “neural net” composed of conjoining neurons
Synaptic clefts- the tiny space between the sending part of one neuron (axon) and the receiving part of another neuron (dendrite).
Neuron doctrine - the theory that the brain is made of many distinct cells called neurons
Electrophysiology - The study of electricity in normal biological function
Motor neurons - One of the three main functional classifications of neurons, along with sensory neurons and interneurons. Motor neurons transmit messages to muscles
Patch-Clamping- a technique in which researchers can record action potentials in individual neurons.
Action Potential- a rapid change in the electrical state of a neuron that is used to convey information in the nervous system.
Resting potential - the normal electrical charge of a neuron relative to the extracellular medium, generally accepted to be about -70mV
Experimental ablation- a technique in which areas are experimentally removed or damaged in order to ascertain their function.
Cytoarchitectural Map- a map of the brain made based on cell types
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Jacob Umans is an aspiring physician-scientist in the Stanford University Class of 2020. As a cofounder of the IYNA, he is passionate about science education and hopes to share his excitement about all subfields of neuroscience -- especially glial biology and neuroimmunity -- with students around the world. He hopes to go on to earn an MD/Ph.D. after graduating from Stanford and to use his clinical experience develop a research focused on developing a better understanding of and improved therapies for neurodegenerative diseases. Outside of neuroscience, Jacob is an avid fan of puns, table tennis, and reading.