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It's important to start with the early findings and studies done in early history before we're able to understand the immense amount of modern-day progression we have made thus far. To discover chemical transmission and the mechanisms of neurotransmitter, it is first important to see how certain aspects of the nervous system were discovered. In this finding, we can observe how Galen had substantial findings on the structure and function of nerves¹. His claims made its way well into the Middle Ages, showing how much of an impact his ideas were¹. We most definitely would not have any of our current knowledge and research without some of Galen's massive discoveries.
Galen, a leading physician of the Roman empire, claimed that the brain was the center for cognition and conscious action. He believed that the nerves stemmed from the brain and also correctly identified that nerves could control the actions of different muscular components². An additional belief he had was that the spinal cord must have been an extending portion of the brain that aided in providing sensation to the rest of the body².
Specifically, he identified that sensory and motor functions must be carried out by 2 different types of nerves². He assigned the soft nerves to be that of sensation and perception, while hard nerves had to be associated with motor abilities. And although his hard/soft nerve claim was wrong, Galen was one of the first to compartmentalize different anatomical structures with functions in the nervous system.
This is especially relevant centuries later, with Sir Bernard Katz's findings, because the function of nerves are the same "vehicles" upon which neurons are able to communicate electrically and chemically. The physiological aspect that Galen found was fundamental for other nervous system research to continue.

Source:
(1) https://pubmed.ncbi.nlm.nih.gov/11618827/
(2) https://web.stanford.edu/class/history13/earlysciencelab/body1/nervespages/nerves.html

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An important advancement was needed before many scientists could get to the point of chemical neurotransmission. This was the advancement of electricity. The knowledge of electricity in the body played a pivotal role in making the future connection with the function of how the brain works on action potentials. This goes hand in hand with the finding of neurotransmitters, as well how electricity and chemicals work together to make the body work.
Luigi Galvani was an Italian physician born in 1737. He focused a lot on anatomical structure of the body, and even began lecturing on frogs.
One day, using a Leyden Jar, he accidentally made his greatest discovery.  Galvani dissected frog legs and noticed that its leg would suddenly kick when a scalpel was placed on exposed nerve¹. Based on several such experiments, Galvani deduced that there was some sort of electricity present in fluid, which he called "animal electricity." To him, the nervous system delivered electrical fluid to the muscle tissue, which produced some sort of effect in the muscle¹. While underdeveloped compared to what is known now about electricity in the body, this was the fundamentally discovery that kickstarted so much of what we know in neuroscience.

Source:
(1)
https://nationalmaglab.org/education/magnet-academy/history-of-electricity-magnetism/pioneers/luigi-galvani

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The Golgi stain revolutionized the way neurons were able to be visualized, and contributed a lot to the knowledge and research of the nervous system. For example, it was able to serve as evidence for the neuron doctrine theory, which had to do with identifying the basic cell unit in the nervous system. It was a fundamental asset in all major discoveries moving forward.
The Golgi stain was developed by Camillo Golgi in 1873¹. Born in Italy in 1843, Golgi studied the nervous system thoroughly and researched upon microscopic structures in tissues and cells. - especially brain cells.
Golgi used silver salts to dye neurons. He hardened brain tissue with potassium dichromate, and then submerged it into silver nitrate solution¹. This silver nitrate solution and potassium dichromate react to form silver chromate along the cell membrane, outlining the cell in black¹. This staining method allowed scientists to visualize entire neurons under the microscope, aiding in more studies upon how its structure correlated to its function.
Sir Bernard Katz work on neurotransmitters and chemical transmission would not be possible if the structure of neurons wasn't known in the first place!

Source:
(1) https://embryo.asu.edu/pages/camillo-golgi-1843-1926

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How were we able to get to the point of understanding chemical transmission the way we do now? What must have helped Sir Bernard Katz in discovering the things he did? First, we can start with the neuron doctrine! In 1873, Camillo Golgi invented a stain, known as the Golgi stain, that allowed for the visualization of nerve cells¹. He proposed the reticular theory, suggesting that all nerve cells were somehow connected.
However, then came neuroscientist Santiago Ramon y Cajal¹. He used the Golgi stain to disprove the reticular theory and come up with something else. He identified the synaptic gaps between neurons and used it to come up with his own hypothesis and eventual theory¹. He claimed that each nerve cell was independent and its own discrete unit, not connected into one entity¹. He saw temporary contact between nerve cells, and that their ends were completely free. Thus, the "neuron doctrine" was formulated.

Source:
(1) https://embryo.asu.edu/pages/neuron-doctrine-1860-1895

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Discovery of Action Potentials: All or None Neural Transmission 

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Discovery of Action Potentials: All or None Neural Transmission 

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Through the demonstration of electricity in animals by Galvani, much was studied and discovered in the course of time after. Many studied the relationship between nerve, muscle tissue, and the electrical connection between both of them. There was a certain strive to figure out the link between electricity and the nervous system. While such studies were helpful, it was hard to find concrete evidence of electrical phenomenas without accurate instruments.  However, in 1865, physiologist Julius Bernstein and Emil du Bois-Reymond problem solved their way through these hindrances with a galvanometer, and were able to record the first time course of an action potential¹. Through these recordings, in 1902, Bernstein proposed a theory of resting and action potentials². He theorized that nerve cells were permeable to certain ions such as potassium, which in turn affect the potential of the cell². For example, he stated that the potassium gradient is what generates a resting potential. Further, he stated that a loss in permeability is what drove an electrical difference to cause an action potential. This aspect of his theory was wrong because in reality, it is actually sodium that impact the cell potential enough to cause an action potential.
Overall, understanding the bio-mechanisms of action potentials was one step forward into the cascade of figuring out the presence of neurotransmitters. Additionally, the knowledge of ions playing a role in electric transmission can also be considered one of the first links between the chemical and electrical importances in the brain.

Sources:
(1) https://www.cell.com/trends/neurosciences/fulltext/0166-2236(83)90078-4
(2) http://amygdala.psychdept.arizona.edu/CompNeuro/Readings/week3/Schuetze+Discovery-action-potential+TINS+1983.pdf

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Development of the Cathode Ray Oscilloscope

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Development of the Cathode Ray Oscilloscope

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For the capacity to understand and research the mechanisms of chemical neurotransmission like Sir Bernard Katz did, it was very important to understand the electrical phenomenon happening behind the scenes. What aids in this, especially in terms of accuracy and precision? Several different tools! One of such tools, for example, was the emergence of the Cathode Ray Oscilloscope. This started with Joseph Erlanger and Herbert Gasser, who were attempting to record nerve impulses¹. And using a cathode ray tube, they succeeded! They saw responses in electrical stimulation through nerves and observed the activity in different fibers with different functions. Additionally, the Cathode Ray Oscilloscope really aided in improving accuracy and precision in its time because it was able to amplify nerve impulses up to 7000x¹. Along with a string electrometer and 3-string amplifier, nerve impulses were able to be visualized.
Additionally, the Cathode Ray Oscilloscope helped in identifying action potentials, which plays a massive role in the transmission of neurotransmitters along the synapse¹.

Source:
(1)  https://oxford.universitypressscholarship.com/view/10.1093/acprof:oso/9780199751754.001.0001/acprof-9780199751754-chapter-006

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George Oliver and his experiment on dogs 

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George Oliver and his experiment on dogs 

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George Oliver, an English physician, who manipulated extracts from the adrenal gland to test the effect and overall function of adrenaline (this substance was not known at the time) in the body. He first experimented by feeding his son adrenal glands to see its effects, and intended on measuring it via a self-made instrument upon the radial artery¹. However, no effects were noted. In current time, we know that this is because adrenaline does not effect the body via oral ingestion¹. His more important contribution, however, is the invention of an instrument that was able to record artery diameter.
Oliver ends up meeting physiologist Edward Sharpey-Schafer, who was injecting adrenal extract into dogs and observing an increase in blood pressure¹. Oliver was able to figure out that injecting the adrenal gland actually elicited a physiological response by causing the artery to narrow significantly.
Soon after this discovery, researchers began trying to identify this substance and it was not until 1901, when Jokichi Takamine was able to isolate the active substance causing a lowering in blood pressure. He decided to name it "adrenaline."

Sources:
(1) http://serious-science.org/adrenaline-7601

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The Discovery of the First Neurotransmitter: Acetylcholine

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The Discovery of the First Neurotransmitter: Acetylcholine

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In 1921, Austrian scientist Otto Leowi designed an experiment that revolutionized the use and impact of neurotransmitters up until this day.
In this experiment, he obtained two frog hearts. "Heart A" was attached to the vagus nerve and contained in a chamber of saline. This chamber was also connected to  another chamber, which contained "Heart B." Upon electrical stimulation of Heart A, Leowi observed that Heart A seemed to have slowed down¹. After a small amount of time, he also noticed that (with no external stimulus), Heart B also slowed down. Thus, he concluded that Heart A's electrical stimulation secreted a chemical substance that also affected the actions of Heart B¹.

This chemical substance is now known as "Acetylcholine" and has many medical uses in today's time. It has the ability to contract smooth muscles, dilate blood vessels, and slow heart rate².

Sources:
(1) http://faculty.washington.edu/chudler/chnt1.html
(2) https://www.britannica.com/science/acetylcholine

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The neuromuscular junction (NMJ) may be one of the most impactful findings on Sir Bernard's work towards the Nobel Prize. Now what is the NMJ? It is a specialized synapse junction between motor neuron nerve and a muscle fiber that can convert electrical impulse from the nerves to activity in the muscle via chemical transmission.
Both Henry Dale and Otto Loewi were awarded a Nobel Prize for their finding on acetylcholine, a neurotransmitter that plays a pivotal role in the NMJ. Dale first isolated the compound in 1913¹. However, they could not link the physiological effects quite yet. It wasn't until beyond the 1930s that chemical transmission came into the picture. This is another reason as to why this discovery was so fundamental to not only Sir Bernard, but also every researcher who was studying the physiological mechanisms of neurotransmitters¹. It proved that while electrical communication was a method of function in the brain, there was much more chemically involved as well.
Itself, the NMJ was an indication that "transmission by chemical mediators" existed due to the presence of acetylcholine there¹.

Source:
(1) https://www.sciencedirect.com/science/article/pii/S1631069106000485?via%3Dihubhttps://www.sciencedirect.com/science/article/pii/S1631069106000485?via%3Dihub

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Vittorio Erspamer, an Italian pharmacologist and scientist, is attributed to discovering the chemical neurotransmitter: serotonin.
He started off with studying various amine substances found on the skin and intestinal tracts within various animal species like rabbits and frogs. Specifically, he focused on a chemical that he found in enterochromaffin cells of the gut¹. He named this chemical "enteramine" and noted its effects on the smooth muscle, as well studying it within other animals. For example, Erspamer studied the appearance of enteramine in the salivary glands of the octopus.
It was only later, around 1952, where it had been found that other scientists were working on the same neurotransmitter, calling it: serotonin¹.
While serotonin may not have been what Sir Bernard Katz was specifically working on, it does contribute to the ongoing research being done at the time on how each chemical compound effects the body in certain ways. In big and small ways, discoveries of all types of neurotransmitters contributed more to the overall specialized functions of these compounds in the body.

Sources:
(1) https://www.nature.com/articles/1395355

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Sir Bernard Katz was a German physiologist who was born in 1911. His work and focus was upon the bio-mechanisms of nerves and muscles. He received his medical degree from the University of Leipzig in 1934, pursued a Ph.D, and even served in the Royal Australian Air Force during World War II. He has written several books, including "Electric Excitation of Nerve" (1939) and "The Release of Neural Transmitter Substances" (1969)¹.
His Nobel Prize winning work was based on the presence of nerve cells and fibers present in both humans and animals². He focused on how impulses in motor neurons can initiate activity and movement in muscles. Specifically, he released studies based on the release of acetylcholine, a neurotransmitter². He found that such impulses can be carried from a nerve fiber to a muscle fiber, winning him a part of the Nobel Prize.

Sources:
(1) https://www.britannica.com/biography/Bernard-Katz
(2) https://www.nobelprize.org/prizes/medicine/1970/katz/facts/

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Electropuncture Treatment as Neuropathic Pain Reliever, involving Excitatory and Inhibitory Neurotransmitter

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Electropuncture Treatment as Neuropathic Pain Reliever, involving Excitatory and Inhibitory Neurotransmitter

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There is still no substantial therapy options for neuropathic pain that is caused by peripheral tissue injuries. Examples of such pain can include numbness, tingling, burning, and other sensations. It is usually caused by a lesion or dysfunction of the somatosensory nervous system, peripherally or centrally. Chronic neuropathic pain actually has some to do with the imbalance of excitatory and inhibitory neurotransmitters¹. Therefore, focusing on restoring these neurotransmitters can be a new approach of treating neuropathic pain¹.
From the study, evidence shows that electroacupuncture can modulate excitatory and inhibitory neurotransmission. Data indicated a reduction of expression in GABA, an inhibitory neurotransmitter, and glutamate, an excitatory neurotransmitter, in the hippocampus¹.  This may modulate neuronal plasticity, which in turn, indicates that perhaps electropuncture may be good at preventing the development of chronic pain.

Source:
(1) https://www.hindawi.com/journals/ecam/2019/6784735/