In 1873 Italy, Camillo Golgi created the black reaction technique, which enabled scientists to stain and view the structure of neurons, the specialized cells that compose the nervous system. During the nineteenth century, scientists were studying cells and proposed cell theory, which describes the basic characteristics of cells as fundamental units of life. However, cell theory struggled to explain neurons as they are specialized cells and more complex in structure than cells of other tissues. Prior to Golgi’s black reaction, other neuron staining techniques did not enable scientists to clearly and completely view entire neurons without damaging the tissue and obscuring the form. By enabling scientists to study individual neurons and neural tissues, Golgi’s black reaction enables researchers to better study the nervous system and how it develops.

Friedrich Tiedemann studied the anatomy of humans and animals in the nineteenth century in Germany. He published on zoological subjects, on the heart of fish, the anatomy of amphibians and echinoderms, and the lymphatic and respiratory system in birds. In addition to his zoological anatomy, Tiedemann, working with the chemist Leopold Gmelin, published about how the digestive system functioned. Towards the end of his career Tiedemann published a comparative anatomy of the brains of white Europeans, black Africans, and Orangutans, in which he argued that there were no appreciable differences between the structure of the brains of blacks, women, and white European men that would suggest they were intellectually different. Tiedemann also researched the embryonic development of the brain and circulatory systems of human fetuses.

In 2011, Sonja Vernes and Simon Fisher performed a series of experiments to determine which developmental processes are controlled by the mouse protein Foxp2. Previous research showed that altering the Foxp2 protein changed how neurons grew, so Vernes and Fisher hypothesized that Foxp2 would affect gene networks that involved in the development of neurons, or nerve cells. Their results confirmed that Foxp2 affected the development of gene networks involved in the growth of neurons, as well as networks that are involved in cell specialization and cell communication. The researchers determined that Foxp2 is important for a variety of developmental processes such as motor control, language acquisition, and cognition.

Scientists use cerebral organoids, which are artificially produced miniature organs that represent embryonic or fetal brains and have many properties similar to them, to help them study developmental disorders like microcephaly. In human embryos, cerebral tissue in the form of neuroectoderm appears within the first nine weeks of human development, and it gives rise to the brain and spinal cord. In the twenty-first century, Juergen Knoblich and Madeleine Lancaster at the Institute of Molecular Biotechnology in Vienna, Austria, grew cerebral organoids from pluripotent stem cells as a model to study developmental disorders in embryonic and fetal brains. One such disorder is microcephaly, a condition in which brain size and the number of neurons in the brain are abnormally small. Scientists use cerebral organoids, which they've grown in labs, because they provide a manipulable model for studying how neural cells migrate during development, the timing of neural development, and how genetic errors can result in developmental disorders.

In the nineteenth century, reticular theory aimed to describe the properties of neurons, the specialized cells which make up the nervous system, but was later disconfirmed by evidence. Reticular theory stated that the nervous system was composed of a continuous network of specialized cells without gaps (synapses), and was first proposed by researcher Joseph von Gerlach in Germany in 1871. Reticular theory played a significant role in developmental neurobiology as it enabled scientists to theorize how the form of neural cells functioned in the context of the broader nervous system, and although disproven, reticular theory contributed to the foundation of the neuron doctrine that informed the modern field of neurobiology.

Camillo Golgi studied the central nervous system during the late nineteenth and early twentieth centuries in Italy, and he developed a staining technique to visualize brain cells. Called the black reaction, Golgi’s staining technique enabled him to see the cellular structure of brain cells, called neurons, with much greater precision. Golgi also used the black reaction to identify structures within animal cells like the internal reticular apparatus that stores, packs, and modifies proteins, later named the Golgi apparatus in his honor. Golgi, along with Santiago Ramón y Cajal, received the Nobel Peace Prize in 1906 for their independent work on the structure of the nervous system. Golgi’s discovery of the black reaction enabled other scientists to better study the structure of the nervous system and its development.

In the early 2000s, Sabata Martino and a team of researchers in Italy and Germany showed that they could reduce the symptoms of Tay-Sachs in afflicted mice by injecting them with a virus that infected their cells with a gene they lacked. Tay-Sachs disease is a fatal degenerative disorder that occurs in infants and causes rapid motor and mental impairment, leading to death at the ages of three to five. In gene therapy, researchers insert normal genes into cells that have missing or defective genes in order to correct genetic disorders. The team created a virus that coded for a specific gene missing in mice with Tay-Sachs. That missing gene is called hexosaminidase subunit alpha (HEXA). Martino and the team injected the virus into the brains of mice with Tay-Sachs in attempt to restore Hexa enzymatic function in the brain and spinal cord (central nervous system).

Roger Wolcott Sperry studied the function of the nervous system in the US during the twentieth century. He studied split-brain patterns in cats and humans that result from separating the two hemispheres of the brain by cutting the corpus callosum, the bridge between the two hemispheres of the brain. He found that separating the corpus callosum the two hemispheres of the brain could not communicate and they performed functions as if the other hemisphere did not exist. Sperry studied optic nerve regeneration through which he developed the chemoaffinity hypothesis. The chemoaffinity hypothesis stated that axons, the long fiber-like process of neurons, connect to their target cells through special chemical markers. This challenged the previously accepted resonance principle of neuronal connection. Sperry shared the 1981 Nobel Prize in Physiology or Medicine with David Hubel and Torsten Wiesel.

In the 1950s and 1960s, Roger Sperry performed experiments on cats, monkeys, and humans to study functional differences between the two hemispheres of the brain in the United States. To do so he studied the corpus callosum, which is a large bundle of neurons that connects the two hemispheres of the brain. Sperry severed the corpus callosum in cats and monkeys to study the function of each side of the brain. He found that if hemispheres were not connected, they functioned independently of one another, which he called a split-brain. The split-brain enabled animals to memorize double the information. Later, Sperry tested the same idea in humans with their corpus callosum severed as treatment for epilepsy, a seizure disorder. He found that the hemispheres in human brains had different functions. The left hemisphere interpreted language but not the right. Sperry shared the Nobel Prize in Physiology or Medicine in 1981for his split-brain research.

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