Walter Eichler and his role in the development of electroneurography.

Walter Eichler (1904-1942) performed the first in situ nerve conduction studies in humans. Eichler's work has been largely overlooked and there have been no biographical accounts written of him. His 1937 paper, Über die Ableitung der Aktionspotentiale vom menschlichen Nerven in situ (On the recording of the action potentials from human nerves in situ) was translated and reviewed. Archival material was obtained on his career that was housed predominantly at the University of Freiburg im Breisgau. He had memberships in Nazi organizations but did not appear to be politically active. During his brief career, he constructed novel equipment and established seminal principles for performing nerve conductions on humans. The authors repeated his experiment in the ulnar nerve, which duplicated Eichler's findings. His recordings were quite remarkable given advances in technology. In summary, the Eichler paper is the first study in the development of in situ clinical electroneurography in humans. Many of his procedural observations are still fundamental in the current practice of electroneurography. As best can be determined, his study in humans did not appear ethically compromised. Although Eichler's personal background remains open to question, his paper is a seminal study in the history and development of clinical electroneurography.Abbreviations: AP: Action potential; C: Capacitor; CNP: Compound nerve potential; DC: Direct current; E1: Preferred term for active electrode; E2: Preferred term for reference electrode; NSDÄB: Nationalsozialistische Deutsche NSD-Ärtzebund (National Socialist German Doctors' League; NSDAP: Nationalsozialistische Deutsche Arbeiterpartei (National Socialist German Workers' Party/ Nazi Party); SS: Schutzstaffel (Protective Echelon or Squad of the Nazi party).

Barbara G. Pickard - Queen of Plant Electrophysiology.

Barbara Gillespie Pickard (1936-2019) studied plant electrophysiology and mechanosensory biology for more than 50 y. Her first papers on the roles of auxin in plant tropisms were coauthored with Kenneth V. Thimann. Later, she studied plant electrophysiology. She made it clear that plant action potentials are not a peculiar feature of so-called sensitive plants, but that all plants exhibit these fast electric signals. Barbara Gillespie Pickard proposed a neuronal model for the spreading of electric signals induced by mechanical stimuli across plant tissues. In later years, she studied the stretch-activated plasma membrane channels of plants and formulated the plasma-membrane control center model. Barbara Pickard summarized all her findings in a new model of phyllotaxis involving waves of auxin fluxes and mechano-sensory signaling.

Part I: The Complex Spikes as One of the Cerebellar Secrets.

The olivocerebellar tract has unique morphological, physiological, and developmental properties. Olivocerebellar axons are the source of multiple climbing fibers (CFs). The synapse between CFs and the Purkinje neuron is one of the most powerful excitatory in the central nervous system. Complex spikes are composed of an initial large amplitude spike followed by spikelets. The spatiotemporal patterns of complex/simple spikes complement the rate coding to enhance the accuracy of motor and cognitive processing, and to improve predictions related to internal models. Understanding the role of complex spikes is essential in clarifying how the cerebellar cortex contributes to learning, motor control, cognitive tasks, and the processing of emotions. This Cerebellar Classic is devoted to the pioneering work of Eccles, Llinás, and Sasaki on complex spikes using intracellular recordings from Purkinje neurons.

Guillaume-Benjamin Duchenne: a miserable life dedicated to science.

Duchenne de Boulogne is known mainly by the disease eponymously named "Duchenne muscular dystrophy", or pseudohypertrophic muscular dystrophy, although some experts consider that the original description of this disease does not belong to him. Less well known are the facts related to the tragic death of his beloved wife shortly after the birth of his only child, the unjustifiable distance he was forced to keep from this son for more than 30 years, and of being humiliated and professionally despised by his peers. These events made the life of this physician, physiologist, researcher and inventor extremely arduous. We emphasize some aspects of the history of this man, his work and his life, a true genius of few friends.

The physiological experiments of Constantin von Economo on the central pathways of mastication and deglutition.

The first study of Constantin von Economo on the mammalian brain was published in 1902. Experiments were carried out in rabbits at the Physiological Institute headed by Siegmund von Exner-Ewarten in Vienna to investigate the central pathways of chewing and swallowing. After placing cortical lesions, Economo applied cortical and subcortical electrical stimulation to obtain masticatory movements, and tracked degenerated fibers by means of the Marchi method. He traced fibers through the internal capsule, ventral nucleus of the thalamus, subthalamic nucleus, substantia nigra and its connections with the motor nucleus of the trigeminal nerve, and nucleus solitarius. He suggested that the substantia nigra is responsible for coordinating alimentation movements, with the involvement of cranial nerves V, VII, IX and X as well. We discuss these findings in a historical and a modern perspective, including the concept of a central pattern generator in the pontine reticular formation and its interaction with the nucleus solitarius. Today we understand that mastication is a voluntary action controlled by motor cortical areas, by motoneurons of the trigeminal, and by a neural pattern generator in the pons. On the other hand, deglutition comprises 'reflex swallowing' triggered by sensory fibers of cranial nerves V, IX and X, and 'voluntary swallowing' which may be controlled by both cortical fields and subcortical areas, such as the internal capsule, the hypothalamus and the mesencephalic reticular formation.

Guillaume-Benjamin Duchenne: a miserable life dedicated to science / Guillaume-Benjamin Duchenne: uma vida de sofrimento dedicada à ciência

ABSTRACT Duchenne de Boulogne is known mainly by the disease eponymously named "Duchenne muscular dystrophy", or pseudohypertrophic muscular dystrophy, although some experts consider that the original description of this disease does not belong to him. Less well known are the facts related to the tragic death of his beloved wife shortly after the birth of his only child, the unjustifiable distance he was forced to keep from this son for more than 30 years, and of being humiliated and professionally despised by his peers. These events made the life of this physician, physiologist, researcher and inventor extremely arduous. We emphasize some aspects of the history of this man, his work and his life, a true genius of few friends.

RESUMO Duchenne de Boulogne é conhecido por muitos principalmente devido à doença que leva seu nome - doença de Duchenne ou Distrofia Muscular Pseudo-hipertrófica - embora alguns historiadores considerem que a descrição original desta doença não lhe pertence. Menos conhecidos são os fatos relacionados à morte trágica de sua amada esposa logo após o nascimento de seu filho, o afastamento injusto que foi forçado a manter deste filho único por mais de 30 anos, e ser humilhado e profissionalmente desprezado por seus pares da comunidade neurológica, que em conjunto tornaram a vida desse médico, fisiologista, pesquisador e inventor, extremamente árdua. Enfatizamos alguns aspectos da história deste homem, seu trabalho e ocaso, protótipo de um verdadeiro gênio de poucos amigos.

Microneurography and sympathetic nerve activity: a decade-by-decade journey across 50 years.

The technique of microneurography has advanced the field of neuroscience for the past 50 years. While there have been a number of reviews on microneurography, this paper takes an objective approach to exploring the impact of microneurography studies. Briefly, Web of Science (Thomson Reuters) was used to identify the highest citation articles over the past 50 years, and key findings are presented in a decade-by-decade highlight. This includes the establishment of microneurography in the 1960s, the acceleration of the technique by Gunnar Wallin in the 1970s, the international collaborations of the 1980s and 1990s, and finally the highest impact studies from 2000 to present. This journey through 50 years of microneurographic research related to peripheral sympathetic nerve activity includes a historical context for several of the laboratory interventions commonly used today (e.g., cold pressor test, mental stress, lower body negative pressure, isometric handgrip, etc.) and how these interventions and experimental approaches have advanced our knowledge of cardiovascular, cardiometabolic, and other human diseases and conditions.

From Bernstein's rheotome to Neher-Sakmann's patch electrode. The action potential.

The aim of this review was to provide an overview of the most important stages in the development of cellular electrophysiology. The period covered starts with Bernstein's formulation of the membrane hypothesis and the measurement of the nerve and muscle action potential. Technical innovations make discoveries possible. This was the case with the use of the squid giant axon, allowing the insertion of "large" intracellular electrodes and derivation of transmembrane potentials. Application of the newly developed voltage clamp method for measuring ionic currents, resulted in the formulation of the ionic theory. At the same time transmembrane measurements were made possible in smaller cells by the introduction of the microelectrode. An improvement of this electrode was the next major (r)evolution. The patch electrode made it possible to descend to the molecular level and record single ionic channel activity. The patch technique has been proven to be exceptionally versatile. In its whole-cell configuration it was the solution to measure voltage clamp currents in small cells. See also: https://doi.org/10.14814/phy2.13860 & https://doi.org/10.14814/phy2.13862.

Electrical coupling and its channels.

As the physiology of synapses began to be explored in the 1950s, it became clear that electrical communication between neurons could not always be explained by chemical transmission. Instead, careful studies pointed to a direct intercellular pathway of current flow and to the anatomical structure that was (eventually) called the gap junction. The mechanism of intercellular current flow was simple compared with chemical transmission, but the consequences of electrical signaling in excitable tissues were not. With the recognition that channels were a means of passive ion movement across membranes, the character and behavior of gap junction channels came under scrutiny. It became evident that these gated channels mediated intercellular transfer of small molecules as well as atomic ions, thereby mediating chemical, as well as electrical, signaling. Members of the responsible protein family in vertebrates-connexins-were cloned and their channels studied by many of the increasingly biophysical techniques that were being applied to other channels. As described here, much of the evolution of the field, from electrical coupling to channel structure-function, has appeared in the pages of the Journal of General Physiology.

Microneurography: how it started and how it works.

In the first section, this historical review describes endeavors to develop the method for recording normal nerve impulse traffic in humans, designated microneurography. The method was developed at the Department of Clinical Neurophysiology of the Academic Hospital in Uppsala, Sweden. Microneurography involves the impalement of a peripheral nerve with a tungsten needle electrode. Electrode position is adjusted by hand until the activity of interest is discriminated. Nothing similar had previously been tried in animal preparations, and thus the large number of preceding studies that recorded afferent activity in other mammals did not offer pertinent methodological guidance. For 2 years, the two scientists involved in the research impaled their own nerves with electrodes to test various kinds of needles and explore different neural systems, all the while carefully watching for signs of nerve damage. Temporary paresthesiae were common, whereas enduring sequelae never followed. Single-unit impulse trains could be discriminated, even those originating from unmyelinated fibers. An explanation for the discrimination of unitary impulses using a coarse electrode is inferred based on the electrical characteristics of the electrode placed in the flesh and the impulse shapes, as discussed in the second section of this paper. Microneurography and the microstimulation of single afferents, combined with psychophysical methods and behavioral tests, have generated new knowledge particularly regarding four neural systems, namely the proprioceptive system, the cutaneous mechanoreceptive system, the cutaneous nociceptive system, and the sympathetic efferent system to skin structures and muscular blood vessels. Examples of achievements based on microneurography are presented in the final section.

From Romanticism and fiction to reality: Dippel, Galvani, Aldini and "the Modern Prometheus". Brief history of nervous impulse / Del romanticismo y la ficción a la realidad: Dippel, Galvani, Aldini y «el moderno Prometeo¼. Breve historia del impulso nervioso.

Mary Wollstonecraft Godwin, better known as Mary Shelley, and her romantic vision of the world gave life to an endless progeny of literacy stories; also originated the myth of the mortal creator who generate life from science. Unexpectedly the history has been considered as a myth, due to acts grounded in facts of certain "truthful;" such were galvanism and the study of the electrical potential in living beings by the two Italian physicians: Luigi Galvani and Giovanni Aldini. Also, is possible to proclaim direct influence on the work by the European folklore surrounding the theologian, alchemist Johann Konrad Dippel and physician who habited the Frankenstein's Castle from his birth, and further developing the "life elixir." The similarities between the novel and the life of the three historical figures suggests that Mary Shelley, belonging to a socially graceful and educated class, was aware of the scientific dispute over the understanding of electricity. Shelley's creative world, full of gothic and romantic hues, shows direct influence of alchemy speaking of the "spark of life" as well as works published by Galvani and Aldini.

Mary Wollstonecraft Godwin (1797-1851), mejor conocida como Mary Shelley, con su visión romántica del mundo dio vida a una progenie interminable de historias en la literatura, y su escrito originó el mito del creador mortal que da vida a partir de la ciencia. Aunque parezca sorprendente, la historia ha llegado a considerarse un mito debido a los actos fundamentados en hechos de cierta forma «verídicos¼ que ayudaron a su origen, como fueron el galvanismo y el estudio del potencial eléctrico en los seres vivos llevados a cabo por dos italianos: Luigi Galvani y Giovanni Aldini. De igual manera, es posible aseverar la influencia directa sobre la obra por parte del folklore europeo de la época que rodeaba al teólogo, alquimista y médico Johann Konrad Dippel, quien hábitó el Castillo Frankenstein desde su nacimiento y además desarrollo el «elixir de la vida¼. La similitud que existe entre la novela y la vida de los tres personajes históricos hace pensar que la autora Mary Shelley, al pertenecer a una clase socialmente agraciada y educada, tuvo conocimiento de la disputa científica por el entendimiento de la energía eléctrica. El mundo creativo de Shelley, lleno de matices góticos y románticos, demuestra influencia directa de la alquimia al hablar de la «chispa de la vida¼, así como de los trabajos publicados por Galvani y Aldini.

The relationship between form and function throughout the history of excitation-contraction coupling.

The concept of excitation-contraction coupling is almost as old as Journal of General Physiology It was understood as early as the 1940s that a series of stereotyped events is responsible for the rapid contraction response of muscle fibers to an initial electrical event at the surface. These early developments, now lost in what seems to be the far past for most young investigators, have provided an endless source of experimental approaches. In this Milestone in Physiology, I describe in detail the experiments and concepts that introduced and established the field of excitation-contraction coupling in skeletal muscle. More recent advances are presented in an abbreviated form, as readers are likely to be familiar with recent work in the field.

Allbutt of Leeds and Duchenne de Boulogne: Newly discovered insights on Duchenne by a British neuropsychiatrist.

It is well-established that Guillaume-Benjamin-Amand Duchenne de Boulogne (1806-1875), and Jean-Martin Charcot (1825-1893) were the founding fathers of Parisian and French neurology during the second half of the 19th century, although much more is known about Charcot than about his "master" Duchenne. In Britain, Thomas Clifford Allbutt (1836-1925) was Leeds' most distinguished physician of the 19th century, eventually becoming Regius Professor of Physic at Cambridge. Allbutt's 1860-1861 year of postgraduate study in Paris and his friendship with Duchenne profoundly influenced his own contributions to nervous system and mental diseases, partly in collaboration with his colleague James Crichton-Browne (1840-1938) at the nearby West Riding Lunatic Asylum in Wakefield, Yorkshire. The present report briefly recalls the careers of Duchenne and Allbutt, and also presents a unique account by Allbutt of Duchenne in action at the height of his powers, investigating and defining the previously uncharted field of neuromuscular diseases with the aid of his localized electrization techniques. This account is discussed in relation to: Duchenne's personality and pioneering neurological achievements; the origins of French neurology; and the development of Anglo-French neurological relationships during the 19th century. Interestingly, both Duchenne and Crichton-Browne separately made important and much-appreciated contributions to the third major book by Charles Darwin (1809-1882), The Expression of the Emotions in Man and Animals, published in 1872.