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Early Understanding of the Nervous System (Pre-1800s)

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Early Understanding of the Nervous System (Pre-1800s)

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Understanding the nervous system before the 19th century wasn't possible. Scientists at that time believed that the nerves were tubes carrying fluids, which were thought to transmit signals from the skin to the brain, and also from the brain to the muscles (1). Anton van Leeuwenhoek was one of the earliest microscopists who made a very significant contribution in saying  that small tube-like structures within compound nerves indicated the cross sections of large myelinated axons (1). But, the issue at the time was that these observations were very limited because of the challenges of studying free tissue, which is soft and hard to dissect. In addition, the early microscopes posed technical limitations, such as optical deviations which decreased how much detail could be seen and couldn’t clearly resolve the fine structures in the nervous structure (1). Because of this, there were incomplete and inaccurate interpretations of the nervous system structure. This early period marked the lack of understanding that cells in the brain and spinal cord are separated, which was not recognized until a couple years later with newer microscopes.

Sources:

https://www.cell.com/current-biology/pdf/S0960-9822(06)01203-6.pdf

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Advancements in Microscopy (Early 1800s)

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Advancements in Microscopy (Early 1800s)

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As the advancement of microscopy began our understanding of cells and the nervous system advanced. In the early 1800s, optical microscopes improved greatly, giving us clearer views of cellular structures. In this period, compound microscopes emerged which combined lenses with different refractive properties which reduced chromatic aberration and increased resolution in the process. This advancement was crucial for the discovery of cells as the basic units of life, which ended up becoming a foundation to biology.  Robert Hooke and Antonie van Leeuwenhoek were very important during this era. Robert Hooke came up with the word “cell” after he saw the structure of the cork, and how porous it was with a light microscope (1). Leeuwenhoek, using more advanced microscopes that will magnify an object 300 times, observed bacteria, sperm, and red blood cells (1). These observations laid the foundation for the cell theory that was proposed a couple years later by  Matthias Schleiden and Theodor Schwann in 1838, which stated that all organisms are composed of cells. Schledin analyzed microscopic studies of plants, and Schwann analyzed animal tissues. From these studies, they arrived at the same conclusion that all organisms are composed of cells, and that cells arise from the division of preexisting cells, rather than de nevo. All in all, the cell became known as the fundamental unit of all living organisms through the discoveries made by light microscopes. The improved microscopes of this period were very essential for the cell theory to arise, because biologists could finally understand the cellular composition of tissues.

Sources:

https://www.ncbi.nlm.nih.gov/books/NBK9941/#:~:text=Contemporary%20light%20microscopes%20are%20able,nuclei%2C%20chloroplasts%2C%20and%20mitochondria.

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"From Purkinje to Golgi: The Roots of Modern Neuroscience" (late 1800s)

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"From Purkinje to Golgi: The Roots of Modern Neuroscience" (late 1800s)

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Jan Evangelista Purkinje was a scientist born in 1787 known for several medical discoveries. One of his key findings was the discovery of large nerve cells in the cerebellum, which are now called Purkinje cells, named after him, how original! These cells are important because they are the ones who assist us in coordinating movement (1). Before his work, scientists at the time did not truly grasp the different types of cells that are in the brain or their distinct functions.  His finding proved that the cerebellum was not just a mass of tissue but it had an organized structure and it had many specific functions (1). Knowing about these cells helped other scientists figure out how nerve cells communicate as well as their function. This was a crucial aspect for the development of the neuron theory, built on Purkinje’s initial observations. Overall, he showed that the brain was made up of specific types of cells, which opened up new ways to study how the brain processes information, controls movements, and regulates various bodily functions through the nervous system (1). His discovery helped others see the brain as a complex system with many interconnected parts that work together.

Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832080/#:~:text=After%20a%20period%20of%20mourning,the%20cerebellum%20(Purkinje%20cells).

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Antonie van Leeuwenhoek discovered tiny organisms which he called "animalcules," through his early microscopes, but no division happening. He claimed that they were appearing spontaneously. This is due to the low quality of the microscopes, but in 1830’s when there were many advancements such as better lenses, higher magnification, and improved lighting, the discovery of the cell theory came to be (1). The cell theory established by Matthias Schleiden and Theodor Schwann in 1838, was a major breakthrough in all of the sciences.  In their works of 1839, they declared that cells are fundamental building blocks for both plants and animals. They also included that some organisms can be single celled, and others can have multiple cells. This theory shifted scientific thought more onto the cellular level. This recognition had many implications on all of the different biological sciences, including neuroscience. It helped scientists understand that the nervous system, like other bodily systems, is made up of cells. The cell theory also motivated further developments in microscopy and histological techniques, and set the stage for the detailed studies of cellular structures and functions that were to come.

Sources:

https://www.britannica.com/science/cell-theory

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Neuron Doctrine vs. Reticular Theory (Late 1800s)

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Neuron Doctrine vs. Reticular Theory (Late 1800s)

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During the late 1800s, the neuron doctrine and the reticular theory became the most important neuroscientific research. The neuron doctrine was proposed by Santiago Ramon y Cajal, who claimed that the nervous system is made up of discrete cellular units called neurons (1). This proposal contradicted the reticular theory that was proposed by Camillo Golgi and a couple other scientists. Golgi claimed that the nervous system was a network of interconnected nerve fibers (1). He later went on to create a method based on a technique for staining nerve cells which was known as the “black reaction.” Through this method he was able to gain a precise description of nerve cells in the cerebro-spinal axis (1). This distinguished the axon from the dendrites. Golgi observed that gray matter was very intricate and dense with branches of axons from the same and different cell layers. Cajal used the same staining method, but his observations yielded different results as he believed that the neuron was the fundamental unit of the nervous system and can act independently (1). The disagreement between the two theories wasn't focused on how different their observations were, but rather they interpreted how the nervous system was structured. Golgi was more focused on a holistic view, and believed that the nervous system was completely interconnected. This perspective aligns with those who challenged the idea of specific brain areas having fixed functions. Cajal, on the other hand held an atomistic-reductionist' view, suggesting that the nervous system is made up of many individual neurons, each with its own anatomy, function, and development, viewing neurons as discrete. This discussion wasn't just about science facts, but also about big ideas on how the brain handles information. The debate was about whether the brain works like a bigger spread-out network, or if it uses specific, separate parts to process things. Eventually, the neuron doctrine was the more accepted concept of neuroscience, as it discussed how neurons communicate through synapses, which helped shape the way scientists look at how the brain works (1).They started to see the brain as having different parts that work together. This new perspective influenced research into brain diseases, how the brain develops as well as neuroplasticity.

Sources: https://pubmed.ncbi.nlm.nih.gov/11640243/

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Camillo Golgi developed a staining technique that would become his most significant contribution, in 1873. This stain is known as the Golgi stain, but also known as the black reaction. This method used potassium dichromate and silver nitrate to visualize neurons and all of their networks in the nervous system (1). This stain provided a tool for detailed observation of individual neurons, which used to be  indistinguishable in unstained brain tissue. This method also revealed the morphologies of neurons and how they are arranged in distinct brain regions, which expands on their functional role. Golgi spent a decade in investigation of the different brain structures, which he then later published in a monograph on the “fine anatomy of the central organs of the nervous system” in 1885 ( 1).

The Golgi staining method became a tool that other scientists used, most famously Ramon y Cajal. Cajal saw Golgi’s method in 1887, over a decade after it was published and was very intrigued. He mentioned in his autobiography that many neurologists either didn't know about the method or didn't think much of it. "He described seeing the stained cells as a transformative moment in his life, like seeing drawings made with black ink"(1).

Golgi then saw Cajal’s success regarding the neuron theory, and so he went back to his lab to refine his staining method. His goal was to make the stains lighter, so that they weren’t as dark. Through this process, in 1898, he discovered a new structure in the spinal ganglia neurons, which he later named the Golgi apparatus (1). In that same year, he discovered the  perineuronal nets, a critical aspect of the  brain's structure.

Golgi continued in his studies of brain tissue well into his later years shown by slides in 1899 that he had signed, and through a photograph of him at his desk in the 1920s surrounded by tissue samples. This shows his dedication and commitment to research and improvement.

Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388087/#:~:text=Golgi's%20%E2%80%9Cblack%20reaction%E2%80%9D%20

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Due to Camillo Golgi’s staining technique a series of discoveries concerning the  nervous system followed. By visualizing neurons in detail, Golgi was able to describe the different types of neurons and their interconnection. Through his work, he realized that neurons were not random in how they were arranged, but they were organized in a specific way with specific pathways and distinct networks (1).This was critical for different brain functions . One of his most significant findings was the  "Golgi type II" short axon cells (1). These axon cells were different from the long axon neurons that they had previously seen. This suggested that there were diverse functions within the brain. Gogli also focused on the cerebellum, which revealed a distinctive arrangement of the neurons, which he named the Golgi cells. These golgi cells provided evidence of synaptic organization of the brain region and challenged many existing views. This also deepended the understanding of how the brain processes information.  In addition to those findings, Golgi explored neuroanatomy in depth and identified the cellular basis of the diseases of the nervous system influencing both clinical neurology and neurological research.

Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769101/

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"Debates That Shaped Neuroscience: Golgi vs. Cajal"

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"Debates That Shaped Neuroscience: Golgi vs. Cajal"

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The scientific debate between Camillo Golgi and Santiago Ramón y Cajal who are two critical figures in the study of neuroscience, in the late 19th and early 20th centuries received their Nobel Prize award in 1906. Taking place within the  academic community and at the Nobel Prize event in Stockholm, Sweden, this debate revolved around Golgi’s support for the reticular theory, which viewed the nervous system as a continuous network, and Cajal’s opposing neuron doctrine, which argued for a system composed of discrete individual cells (1). This was a significant moment in neuroscience history, because it focuses on the exchange of ideas between Golgi and Cajal, and how that brought upon more research and discussion. The debates shows how important scientific progress is, and how having conflicting views can do more good than bad. It also played a critical role in establishing the concepts that influence modern neuroscience from studying neural networks to exploring neurodegenerative disease.

Sources: https://www.cell.com/current-biology/pdf/S0960-9822(06)01203-6.pdf

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How Vesalius' Drawings Paved the Way for Golgi's Neurological Breakthroughs" (1543)

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How Vesalius' Drawings Paved the Way for Golgi's Neurological Breakthroughs" (1543)

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Andreas Vesalius was born in Brussels in 1514 and became a critical figure in the history of medicine and neuroscience. One of his most important works is the "De humani corporis fabrica," which contained many anatomical studies published in 1543. He did not rely on texts of Galen or any other past scientist, he wanted to do direct observation himself through dissections, which was a bold move at the time (1). He dissected bodies, which was rare because the professor at the time would read from the book and have an assistant do the messy work, but Vesalius wanted to be hands on. Through this approach, he was able to create highly detailed and accurate anatomical drawings. Before Vesalius, much of  what was believed about human anatomy was based on animal dissection, so there were a great deal of ideas incorrectly stated prior to Vesalius studies. When Vesalius published his illustrations, he showed that Galen’s animal-based anatomy didn’t always apply to humans, correcting several misconceptions (1). This move away from relying solely on ancient texts and towards empirical evidence laid the groundwork for modern anatomy and medicine. Vesalius' emphasis on detailed anatomical drawings influenced loads of other scientists, like Camillo Golgi.

Sources: 1.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966481/

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762440/

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Camillo Golgi’s Early Life and Education (1843-1865)

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Camillo Golgi’s Early Life and Education (1843-1865)

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Camillo Golgi, born in 1843 in Corteno, Italy was directed towards medicine because of his physican father. He went to the University of Pavia where his academic journey was shaped by notable mentors including Cesare Lombroso, an Italian psychiatrist, and Giulio Bizzozero, a physician who introduced him to histological techniques (1). Golgi only went into medicine to support his family through his medical practice but later on a growing intrest of research in the nervous system and microscopic techniques took him in. His early work, including his focus on mental illness showed his fascination with the structure of the brain and function.

Golgi did have many financial problems, and did not have a stable position at his university so he became a a chief physician at Pio Luogo degli Incurabili in Abbiategrasso, Italy, in 1872 (1). It was there that he developed his famous Black Reaction staining method in his kitchen which changed the study of the nervous system. His persistence and innovative approach made him a key figure in neuroscience and later led to win a Nobel Prize in Physiology or Medicine with Santiago Ramón y Cajal.

In addition to all of this, Golgi held several positions,  including Rector of the University of Pavia, and served as an advisor at international universities. He also participated in multiple scientific academies and during World War I, directed a military hospital in Pavia (1). Then he retired in 1918, but was still a Professor Emeritus at Pavia (1).

Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769101/

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In 1906, Camillo Golgi and Santiago Ramon y Cajal were awarded the Nobel  Prize in Physiology or Medicine together. They were rewarded this prize for their studies of the structure of the nervous system. This award was an extremely significant acknowledgement of their contributions to the neuroscience field, and in recognizing how important their discoveries were to the medical and scientific communities around them. The Nobel Prize ceremony really highlighted how important their research was in helping us understand how the brain and nerves work. Even though Golgi didn't completely agree with the popular theories about neurons, he accepted the prize, showing he really cared about pushing science forward. His Nobel Lecture was ironically called "The Neuron Doctrine," which showed both his contributions and the odd situation of winning the prize with Cajal, who he didn't always agree with. This event was a big deal in the history of studying the brain, honoring two important scientists whose work has helped shape what we know about neuroscience today.

Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388087/#:~:text=Golgi's%20%E2%80%9Cblack%20reaction%E2%80%9D%20

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Bridging Golgi's Techniques with Modern Neuroscience

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Bridging Golgi's Techniques with Modern Neuroscience

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The Golgi staining technique has significantly influenced modern neuroscience. His technique was used to visualize the detailed structures of neurons, which is how we gained our understanding of how the brain functions and also various diseases that can arise. The relevance of Golgi staining continues as it is being integrated with advanced technologies such as

fluorescent labeling, tissue clearing, and 3D electron microscopy.  Fluorescent labeling is used by researchers by combining Golgi staining with fluorescent dyes to label different types of brain cells or specific proteins within neurons. This helps contrast the dense Golgi images with specific markers which are illuminated by the fluorescence. Techniques like CLARITY and iDISCO make tissue samples transparent by reducing light scattering (1). In addition to this, they help form more detailed imaging of the structures using light microscopy. When combined with Golgi staining, this allows for visualization of neurons throughout a larger volume of tissue. Using  3D electron microscopy allows scientists to see specific structural details of neurons providing high resolution images, and insights into the cellular processes (1 ). These enhanced versions of Golgi staining are being used in many research labs to investigate neuronal morphology and the complexity of the brain. There is a specific focus on complex brain diseases such as Alzheimer’s.  By applying modified Golgi staining in models of Alzheimer’s disease, researchers can observe changes in neuronal structure and connectivity that occur during the disease (1). This helps us understand how Alzheimer's affects brain architecture leading to a potential therapy. In addition to Alzheimer’s, these methods will help guide us in the study of different neurodevelopmental and neurodegenerative diseases such as Parkinson's and schizophrenia. I thought this was really interesting because Golgi staining is still being used today and only with minimal improvements which highlights how important the discovery of his theory was, making Golgi a legacy in the field and exploration of neuroscience.

Source: https://www.nature.com/articles/s41598-018-37377-x#:~:text=Today%2C%20Golgi%20staining%20techniques%20are,dense%20silver%20deposits%2C%20which%20mask