History of neuroscience

From Wikipedia, the free encyclopedia

People throughout the period 5000 years of recorded history have remained divided between the heart and the brain as the workstation of intelligence. Initially it was the heart that dominated the scene. According to Herodotus, in ancient Egypt, they used to remove the brain from the body as a stuffing of some sort in preparation for mummification and the next intellectual life, evidently considering the heart sufficient for this purpose. The view has reversed in the recent times when the brain is identified to be the seat of intelligence, though the heart for its presumed involvement in intelligence still occupy the debate, more definitely, the languages describing intelligent work, for example, "memorizing by heart".


Hieroglyph designating the brain or skull in the Edwin Smith papyrus

The earliest reference to the brain occurs in the Edwin Smith Surgical Papyrus, written in the 17th century BC. The hieroglyph for brain, occurring eight times in this papyrus, describes the symptoms, diagnosis, and prognosis of two patients, wounded in the head, having their skulls fractured. The assessments of the author (a battlefield surgeon) of the papyrus allude to ancient Egyptians having a vague recognition of the effects of head trauma. The author of the passage noted "the pulsations of the exposed brain" and compared the surface of the brain to the rippling surface of copper slag. The location of the injury was related to the laterality of symptoms of aphasia ("he speaks not to thee") and seizures ("he shudders exceedingly"). Against the background medical knowledge of the time based on myths and superstition, the battlefield surgeon applied empirical methods and logical deduction.[1][2]

In Ancient Greece, interest in the brain began with the work of Alcmaeon, who dissected the eye and related vision to the brain. He also suggested that the brain, not the heart, was the organ that ruled the body (what Stoics would call the hegemonikon). It supported the senses and acted as the seat of memories and thought.[2] The author of On the Sacred Disease also believed the brain to be the seat of intelligence.

On the contrary, in the 4th century BC, Aristotle thought that the heart was the seat of intelligence, while the brain was merely a station for cooling the blood. He reasoned that humans are more rational than the beasts because, among other things, they have a larger brain to cool their hot-bloodedness (hot-headedness).[3] During the Hellenistic period, Herophilus and Erasistratus of Alexandria engaged in studies that involved dissecting human bodies, providing evidence for the primacy of the brain. They even made a distinction based on functions between the two major parts of the brain, the cerebrum and the cerebellum. Their works are now mostly lost, but some of their work was re-discovered posthumously .[2]

During the time of Roman Empire, a Greek physician and philosopher Galen dissected the brains of oxen, Barbary apes, swine, and other non-human mammals. He concluded that the cerebellum, being denser part of the brain, controlled the muscles, while the cerebrum being soft must be the seat of intellectual activities. In 19th century, François Magendie and Charles Bell progressed he understanding Galen on connection of the brain with the spinal function.[2][3]

Medieval to early modern[edit]

Islamic medicine in the middle ages focused on how the mind and body interacted with the emphasis on the need to understand mental health. Circa 1000, Al-Zahrawi from Islamic Iberia evaluated neurological patients and performed surgical treatments of head injuries, skull fractures, spinal injuries, hydrocephalus, subdural effusions and headache.[4] In Persia, Avicenna (Ibn-Sina) presented detailed knowledge about skull fractures and their surgical treatments.[5] Avicenna is generally regarded as the father of early modern medicine.[6][7][8] He wrote 40 pieces on medicine, with the most notable being the Qanun, a medical encyclopedia that would become a staple at universities for nearly 100 years. He also explained phenomena such as insomnia, mania, hallucinations, nightmares, dementia, epilepsy, stroke, paralysis, vertigo, melancholia and tremors, and discovered a condition similar to schizophrenia (Junun Mufrit). Avicenna also named parts of the brain and discovered their functions, and associated specific mental deficits with defects in certain part of the brain.[9] Abulcasis, Averroes, Avenzoar, and Maimonides, active in the Medieval Muslim and Jewish worlds, also described a number of medical problems related to the brain.

Between the 13th and 14th centuries, the first anatomy textbooks in Europe, which included a description of the brain, were written by Mondino de Luzzi and Guido da Vigevano.[10][11]


One of Leonardo da Vinci's sketches of the human skull

Work by Andreas Vesalius on human cadavers found problems with the Galenic view of anatomy. Vesalius noted many structural characteristics of the brain and the nervous system during his dissections.[12] Vesalius proposed that the brain was made up of seven pairs of 'brain nerves', each with a specialized set of functions. Other scholars furthered Vesalius' work by adding their own detailed sketches of the brain.

Scientific Revolution[edit]

In the 17th century, René Descartes studied the physiology of the brain, proposing the theory of dualism to tackle the issue of the brain's relation to the mind. He even suggested a place called the pineal gland in the brain where the mind interacted with the body. Thomas Willis studied the brain, nerves, and behavior to develop neurologic treatments. He described in great detail the structure of the brain: the brainstem, the cerebellum, the ventricles, and the cerebral hemispheres.

Modern period[edit]

The passage of electric current along the nerves was first observed in dissected frogs by Luigi Galvani, Lucia Galeazzi Galvani and Giovanni Aldini in the second half of the 18th century. In 1811, César Julien Jean Legallois described a specific part of the brain, the medulla oblongata involved in respiration in animals.[13] Between 1811 and 1824, Charles Bell and François Magendie discovered the arrangement of receiving and sending messages in the spinal nerves: the ventral roots in spine transmitting motor impulses and the posterior roots receiving sensory input (Bell–Magendie law).[14] In the 1820s, Jean Pierre Flourens pioneered the experimental method of carrying out localized lesions of the brain in animals describing their effects on motricity, sensibility and behavior. He concluded that the ablation of the cerebellum resulted in movements that “were not regular and coordinated".[15] At mid century, Emil du Bois-Reymond, Johannes Peter Müller, and Hermann von Helmholtz showed neurons were electrically excitable and that their activity predictably affected the electrical state of adjacent neurons.[16]

In 1848, John Martyn Harlow described that Phineas Gage had his frontal lobe pierced by an iron tamping rod in a blasting accident. He became a case study in the connection between the prefrontal cortex and executive functions.[17] In 1861, Paul Broca heard of a patient at the Bicêtre Hospital who had a 21-year progressive loss of speech and paralysis but neither a loss of comprehension nor mental function. Broca performed an autopsy and determined that the patient had a lesion in the frontal lobe in the left cerebral hemisphere. Broca published his findings from the autopsies of twelve patients in 1865. His work inspired others to perform careful autopsies with the aim of linking more brain regions to sensory and motor functions. Another French neurologist, Marc Dax, made similar observations a generation earlier.[18] Broca's hypothesis was supported by Gustav Fritsch and Eduard Hitzig who discovered in 1870 that electrical stimulation of motor cortex caused involuntary muscular contractions of specific parts of a dog's body and by observations of epileptic patients conducted by John Hughlings Jackson, who correctly deduced in the 1870s the organization of the motor cortex by watching the progression of seizures through the body. Carl Wernicke further developed the theory of the specialization of specific brain structures in language comprehension and production. Richard Caton presented his findings in 1875 about electrical phenomena of the cerebral hemispheres of rabbits and monkeys. In 1878, Hermann Munk found in dogs and monkeys that vision was localized in the occipital cortical area,[19] David Ferrier found in 1881 that audition was localized in the superior temporal gyrus and Harvey Cushing found in 1909 that the sense of touch was localized in the postcentral gyrus.[20] Modern research still uses the Korbinian Brodmann's cytoarchitectonic (referring to study of cell structure) anatomical definitions from this era in continuing to show that distinct areas of the cortex are activated in the execution of specific tasks.[18]

Studies of the brain became more sophisticated after the invention of the microscope and the development of a staining procedure by Camillo Golgi during the late 1890s that used a silver chromate salt to reveal the intricate structures of single neurons. His technique was used by Santiago Ramón y Cajal and led to the formation of the neuron doctrine, the hypothesis that the functional unit of the brain is the neuron. Golgi and Ramón y Cajal shared the Nobel Prize in Physiology or Medicine in 1906 for their extensive observations, descriptions and categorizations of neurons throughout the brain. The hypotheses of the neuron doctrine were supported by experiments following Galvani's pioneering work in the electrical excitability of muscles and neurons. In 1898, British scientist John Newport Langley first coined the term "autonomic" in classifying the connections of nerve fibers to peripheral nerve cells.[21] Langley is known as one of the fathers of the chemical receptor theory, and as the origin of the concept of "receptive substance".[22][23] Towards the end of the nineteenth century Francis Gotch conducted several experiments on nervous system function. In 1899 he described the "inexcitable" or "refractory phase" that takes place between nerve impulses. His primary focus was on how nerve interaction affected the muscles and eyes.[24]

Heinrich Obersteiner in 1887 founded the ‘‘Institute for Anatomy and Physiology of the CNS’’, later called Neurological or Obersteiner Institute of the Vienna University School of Medicine. It was one of the first brain research institutions in the world. He studied the cerebellar cortex, described the Redlich–Obersteiner's zone and wrote one of the first books on neuroanatomy in 1888. Róbert Bárány, who worked on the physiology and pathology of the vestibular apparatus, attended this school, graduating in 1900. Obersteiner was later superseded by Otto Marburg.[25]

Twentieth century[edit]

Neuroscience during the twentieth century began to be recognized as a distinct unified academic discipline, rather than studies of the nervous system being a factor of science belonging to a variety of disciplines.

Ivan Pavlov contributed to many areas of neurophysiology. Most of his work involved research in temperament, conditioning and involuntary reflex actions. In 1891, Pavlov was invited to the Institute of Experimental Medicine in St. Petersburg to organize and direct the Department of Physiology.[26] He published The Work of the Digestive Glands in 1897, after 12 years of research. His experiments earned him the 1904 Nobel Prize in Physiology and Medicine. During the same period, Vladimir Bekhterev discovered 15 new reflexes and is known for his competition with Pavlov regarding the study of conditioned reflexes. He founded the Psychoneurological Institute at the St. Petersburg State Medical Academy in 1907 where he worked with Alexandre Dogiel. In the institute, he attempted to establish a multidisciplinary approach to brain exploration.[27] The Institute of Higher Nervous Activity in Moscow, Russia was established on July 14, 1950.

Charles Scott Sherrington's work focused strongly on reflexes and his experiments led up to the discovery of motor units. His concepts centered around unitary behaviour of cells activated or inhibited at what he called synapses. Sherrington received the Nobel prize for showing that reflexes require integrated activation and demonstrated reciprocal innervation of muscles (Sherrington's law).[28][29][30] Sherrington also worked with Thomas Graham Brown who developed one of the first ideas about central pattern generators in 1911. Brown recognized that the basic pattern of stepping can be produced by the spinal cord without the need of descending commands from the cortex.[31][32]

Acetylcholine was the first neurotransmitter to be identified. It was first identified in 1915 by Henry Hallett Dale for its actions on heart tissue. It was confirmed as a neurotransmitter in 1921 by Otto Loewi in Graz. Loewi demonstrated the ″humorale Übertragbarkeit der Herznervenwirkung″ first in amphibians.[33] He initially gave it the name Vagusstoff because it was released from the vagus nerve and in 1936 he wrote:[34] ″I no longer hesitate to identify the Sympathicusstoff with adrenaline.″

A graph showing the threshold for nervous system response

One major question for neuroscientists in the early twentieth century was the physiology of nerve impulses. In 1902 and again in 1912, Julius Bernstein advanced the hypothesis that the action potential resulted from a change in the permeability of the axonal membrane to ions.[35][36] Bernstein was also the first to introduce the Nernst equation for resting potential across the membrane. In 1907, Louis Lapicque suggested that the action potential was generated as a threshold was crossed,[37] what would be later shown as a product of the dynamical systems of ionic conductances. A great deal of study on sensory organs and the function of nerve cells was conducted by British physiologist Keith Lucas and his protege Edgar Adrian. Keith Lucas' experiments in the first decade of the twentieth century proved that muscles contract entirely or not at all, this was referred to as the all-or-none principle.[38] Edgar Adrian observed nerve fibers in action during his experiments on frogs. This proved that scientists could study nervous system function directly, not just indirectly. This led to a rapid increase in the variety of experiments conducted in the field of neurophysiology and innovation in the technology necessary for these experiments. Much of Adrian's early research was inspired by studying the way vacuum tubes intercepted and enhanced coded messages.[39] Concurrently, Josepht Erlanger and Herbert Gasser were able to modify an oscilloscope to run at low voltages and were able to observe that action potentials occurred in two phases—a spike followed by an after-spike. They discovered that nerves were found in many forms, each with their own potential for excitability. With this research, the pair discovered that the velocity of action potentials was directly proportional to the diameter of the nerve fiber and received a Nobel Prize for their work.[40]

Kenneth Cole joined Columbia University in 1937 and remained there until 1946 where he made pioneering advances modelling the electrical properties of nervous tissue. Bernstein's hypothesis about the action potential was confirmed by Cole and Howard Curtis, who showed that membrane conductance increases during an action potential.[41] David E. Goldman worked with Cole and derived the Goldman equation in 1943 at Columbia University.[42][43] Alan Lloyd Hodgkin spent a year (1937–38) at the Rockefeller Institute, during which he joined Cole to measure the D.C. resistance of the membrane of the squid giant axon in the resting state. In 1939 they began using internal electrodes inside the giant nerve fibre of the squid and Cole developed the voltage clamp technique in 1947. Hodgkin and Andrew Huxley later presented a mathematical model for transmission of electrical signals in neurons of the giant axon of a squid and how they are initiated and propagated, known as the Hodgkin–Huxley model. In 1961–1962, Richard FitzHugh and J. Nagumo simplified Hodgkin–Huxley, in what is called the FitzHugh–Nagumo model. In 1962, Bernard Katz modeled neurotransmission across the space between neurons known as synapses. Beginning in 1966, Eric Kandel and collaborators examined biochemical changes in neurons associated with learning and memory storage in Aplysia. In 1981 Catherine Morris and Harold Lecar combined these models in the Morris–Lecar model. Such increasingly quantitative work gave rise to numerous biological neuron models and models of neural computation.

Eric Kandel and collaborators have cited David Rioch, Francis O. Schmitt, and Stephen Kuffler as having played critical roles in establishing the field.[44] Rioch originated the integration of basic anatomical and physiological research with clinical psychiatry at the Walter Reed Army Institute of Research, starting in the 1950s. During the same period, Schmitt established a neuroscience research program within the Biology Department at the Massachusetts Institute of Technology, bringing together biology, chemistry, physics, and mathematics. The first freestanding neuroscience department (then called Psychobiology) was founded in 1964 at the University of California, Irvine by James L. McGaugh. Stephen Kuffler started the Department of Neurobiology at Harvard Medical School in 1966. The first official use of the word "Neuroscience" may be in 1962 with Francis O. Schmitt's "Neuroscience Research Program", which was hosted by the Massachusetts Institute of Technology.[45]

Over time, brain research has gone through philosophical, experimental, and theoretical phases, with work on brain simulation predicted to be important in the future.[46]

Institutes and organizations[edit]

As a result of the increasing interest about the nervous system, several prominent neuroscience institutes and organizations have been formed to provide a forum to all neuroscientists. The largest professional neuroscience organization is the Society for Neuroscience (SFN), which is based in the United States but includes many members from other countries.

List of the major institutes and organizations
Foundation Institute or organization
1887 Obersteiner Institute of the Vienna University School of Medicine[47]
1903 The brain commission of the International Association of Academies[48]
1907 Psychoneurological Institute at the St. Petersburg State Medical Academy
1909 Netherlands Central Institute for Brain Research in Amsterdam, now Netherlands Institute for Neuroscience
1947 National Institute of Mental Health and Neurosciences
1950 Institute of Higher Nervous Activity
1960 International Brain Research Organization
1963 International Society for Neurochemistry
1968 European Brain and Behaviour Society
1968 British Neuroscience Association[49]
1969 Society for Neuroscience
1997 National Brain Research Centre

In 2013, the BRAIN Initiative was announced in the US. An International Brain Initiative was created in 2017,[50] currently integrated by more than seven national-level brain research initiatives (US, Europe, Allen Institute, Japan, China, Australia, Canada, Korea, Israel)[51] spanning four continents.

See also[edit]


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Further reading[edit]

  • Rousseau, George S. (2004). Nervous Acts: Essays on Literature, Culture and Sensibility. Basingstoke: Palgrave Macmillan. ISBN 1-4039-3454-1 (Paperback) ISBN 1-4039-3453-3
  • Wickens, Andrew P. (2015) A History of the Brain: From Stone Age Surgery to Modern Neuroscience. London: Psychology Press. ISBN 978-1-84872-365-8 (Paperback), 978-84872-364-1 (Hardback), 978-1-315-79454-9 (Ebook)

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