Ricardo Miledi
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Ricardo Miledi (15 September 1927 – 18 December 2017) was a Mexican
neuroscientist A neuroscientist (or neurobiologist) is a scientist specializing in neuroscience that deals with the anatomy and function of neurons, Biological neural network, neural circuits, and glia, and their Behavior, behavioral, biological, and psycholo ...
known for his work deciphering the role of
calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
in
neurotransmitter release Exocytosis is a term for the active transport process that transports large molecules from cell to the extracellular area. Hormones, proteins and neurotransmitters are examples of large molecules that can be transported out of the cell. Exocytosis ...
. He also helped to develop a technique for studying native receptors in frog oocytes for drug development.


Life

One of seven children, he received undergraduate and medical degrees at National Autonomous University of Mexico (UNAM). While in medical school, he decided that he would make a "terrible clinician", as "he imagined that he would end up seeing only one patient per week, because he would always be too interested in every unknown detail of the case, trying to work out how medicines might act." As a result, when required to perform social service as a component of his training in medical school, he chose a research fellowship at the "Instituto Nacional de Cardiología" under Arturo Rosenblueth. There, he studied the electrical origins of ventricular fibrillation and became skilled at delicate laboratory work. In 1955, he spent a summer at the
Marine Biological Laboratory The Marine Biological Laboratory (MBL) is an international center for research and education in biological and environmental science. Founded in Woods Hole, Massachusetts, in 1888, the MBL is a private, nonprofit institution that was independent ...
at Wood's Hole. There, he began his study of synapses in the common squid and began to see the importance of calcium in synaptic transmission. Around 1956/1957 Miledi conducted research in Canberra, Australia. In 1958, he met frequent collaborator, Noble Laureate
Bernard Katz Sir Bernard Katz, FRS (; 26 March 1911 – 20 April 2003) was a German-born British physician and biophysicist, noted for his work on nerve physiology; specifically, for his work on synaptic transmission at the nerve-muscle junction. He share ...
, who offered him a position in the Department of Biophysics at
University College London University College London (Trade name, branded as UCL) is a Public university, public research university in London, England. It is a Member institutions of the University of London, member institution of the Federal university, federal Uni ...
. There, he studied the release of
Acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
(ACh) and the expression of its receptors. From these studies, he introduced evidence of a phenomenon known as spillover, in which neurotransmitters diffuse away and stimulate extrasynaptic receptors. Further work on extrasynaptic receptors led to the development of the concept of
neuromodulation Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a sec ...
. This laid the groundwork for future studies in
neurotrophic factors Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and cell differentiation, differentiation of both developing and mature neurons. Most ...
, which would ultimately lead to his work in
denervation Denervation is any loss of nerve supply regardless of the cause. If the nerves lost to denervation are part of neural communication to an organ system or for a specific tissue function, alterations to or compromise of physiological functioning ca ...
. By studying denervation in frog skeletal muscle, it was discovered that glial cells, particularly Schwann cells, behave as neurotrophic factors by taking on neuronal activity and releasing Acetylcholine themselves in order to preserve the neuromuscular junction.In the early 1960s, he again became interested in the role of calcium. He found that "in zero-Ca2+ medium, the nerve impulse still fully invades the nerve terminal, but does not release any neurotransmitter. And then as soon as you give a little Ca2+, you get neurotransmitter release." He and Katz published a paper establishing the major role of Ca2+ in ACh release. Further work with squid contributed to an even better understanding of the role of Ca2+ in neurotransmitter release. Miledi was elected as a fellow to the British
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
in 1970. During the early 1970s Miledi was a frequent research scientist during the summer months at the Stazione Zoologica in Naples, Italy ostensibly as the local squid made excellent research specimens. He is also one of the 42 founding fellows of
The World Academy of Sciences The World Academy of Sciences for the advancement of science in developing countries (TWAS) is a North–south research partnerships, merit-based science academy established for developing countries, uniting more than 1,400 scientists in some 1 ...
in 1983, to recognize outstanding scientists from developing countries and honour their achievements in research and development. Miledi was a Distinguished Professor at
University of California, Irvine The University of California, Irvine (UCI or UC Irvine) is a Public university, public Land-grant university, land-grant research university in Irvine, California, United States. One of the ten campuses of the University of California system, U ...
; having joined the faculty in the early 1980s. While there, he spent time developing a technique called microtransplantation, which would allow researchers to study receptors from postmortem diseased human brain tissue in a functional model. He developed this technique based on earlier work in which he performed the first electrophysiological recording of a frog
oocyte An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...
, discovering its inherent property of already having neurotransmitter receptors. From the 1990s until his death he was Distinguished Professor at
UNAM The National Autonomous University of Mexico (, UNAM) is a public research university in Mexico. It has several campuses in Mexico City, and many others in various locations across Mexico, as well as a presence in nine countries. It also has 34 ...
's Institute of Neurobiology, in
Querétaro Querétaro, officially the Free and Sovereign State of Querétaro, is one of the Political divisions of Mexico, 32 federal entities of Mexico. It is divided into Municipalities of Querétaro, 18 municipalities. Its capital city is Querétaro Cit ...
, Mexico. His awards include the
Royal Medal The Royal Medal, also known as The Queen's Medal and The King's Medal (depending on the gender of the monarch at the time of the award), is a silver-gilt medal, of which three are awarded each year by the Royal Society. Two are given for "the mo ...
(1998), the
King Faisal International Prize The King Faisal Prize (, formerly King Faisal International Prize), is an annual award sponsored by King Faisal Foundation presented to "dedicated men and women whose contributions make a positive difference". The foundation awards prizes in fiv ...
for Science (1988), the
Prince of Asturias Award The Princess of Asturias Awards (, ), formerly the Prince of Asturias Awards from 1981 to 2014 (), are a series of annual prizes awarded in Spain by the Princess of Asturias Foundation (previously the Prince of Asturias Foundation) to individuals ...
(1999), and the Society for Neuroscience's Ralph W. Gerard Prize for outstanding contributions to the field (2010).


See also

*
Rodolfo Llinás Rodolfo Llinás Riascos (born 16 December 1934) is a Colombian neuroscientist. He is currently the Thomas and Suzanne Murphy Professor of Neuroscience and Chairman Emeritus of the Department of Physiology & Neuroscience at the NYU School of Me ...
* Stazione Zoologica Napoli


References


External links

* {{DEFAULTSORT:Miledi, Ricardo 1927 births 2017 deaths Royal Medal winners Mexican neuroscientists Fellows of the Royal Society Members of the United States National Academy of Sciences National Autonomous University of Mexico alumni Mexican expatriates in the United Kingdom Mexican expatriates in the United States University of California, Irvine faculty Academic staff of the National Autonomous University of Mexico