Making the Brain Plastic: Early Neuroanatomical Staining Techniques and the Pursuit of Structural Plasticity, 1910–1970

The concept of neuronal plasticity is widely used, but seldom defined in the neurosciences. It can signify many different occurrences, such as structural alterations of axons and dendrites (Cotman & Nadler, 1978), behavioural adaptations (Rosenzweig & Bennett, 1996), or physiological changes in synapse formation (Martin et al., 2000) at different stages of health and disease. Although there is such a wealth of research from many disciplines, the neuroanatomical aspects of plasticity are the focus of this paper. It seeks to illuminate the evolution of different concepts of plasticity concerning the structure and circuitry of the central nervous system (CNS). Early modern morphological research on de- and regeneration phenomena in the 19th- and early 20th-century is well documented. These studies, however, almost exclusively concentrated on the peripheral nervous system (PNS). It was one of the major contributions of Santiago Ramón y Cajal (1852–1934), that he applied the concept of regenerative capacities to the CNS. But the term plasticity seemed to have disappeared for about two decades after his death. The ensuing comeback of the expression may be attributed, at least in part, to new neuroanatomical staining and tracing methods. The pursuit of these techniques will serve as a guidepost through varying approaches in different times: It was the 1950s which seemed to spawn the time for new departures in structural investigations of neuronal plasticity.     

The origin of the term plasticity in the neurosciences: Ernesto Lugaro and chemical synaptic transmission

The Italian psychiatrist Ernesto Lugaro can be regarded as responsible for introducing the term plasticity into the neurosciences as early as 1906. By this term he meant that throughout life the anatomo-functional relations between neurons can change in an adaptive fashion to enable psychic maturation, learning, and even functional recovery after brain damage. Lugaro's concept of plasticity was strongly inspired by a neural hypothesis of learning and memory put forward in 1893 by his teacher Eugenio Tanzi. Tanzi postulated that practice and experience promote neuronal growth and shorten the minute spatial gaps between functionally associated neurons, thus facilitating their interactions. In addition to discovering the cerebellar cells known by his name and advancing profound speculations about the functions of the glia, Lugaro lucidly foresaw the chemical nature of synaptic transmission in the central nervous system, and was the first to propose the usage of the terms "nervous conduction" and "nervous transmission" in their currently accepted meaning.     

The Origin of the Term Plasticity in the Neurosciences: Ernesto Lugaro and Chemical Synaptic Transmission

The Italian psychiatrist Ernesto Lugaro can be regarded as responsible for introducing the term plasticity into the neurosciences as early as 1906. By this term he meant that throughout life the anatomo-functional relations between neurons can change in an adaptive fashion to enable psychic maturation, learning, and even functional recovery after brain damage. Lugaro’s concept of plasticity was strongly inspired by a neural hypothesis of learning and memory put forward in 1893 by his teacher Eugenio Tanzi. Tanzi postulated that practice and experience promote neuronal growth and shorten the minute spatial gaps between functionally associated neurons, thus facilitating their interactions. In addition to discovering the cerebellar cells known by his name and advancing profound speculations about the functions of the glia, Lugaro lucidly foresaw the chemical nature of Synaptic transmission in the central nervous system, and was the first to propose the usage of the terms “nervous conduction” and “nervous transmission” in their currently accepted meaning.     

Mesoglia & microglia--a historical review of the concept of mononuclear phagocytes within the central nervous system

More than a century and a half has elapsed since the first accounts of mesodermal phagocytic elements were proposed within the central nervous system. Over the intervening decades, body and substance were added to this concept through the advancement of histological techniques at the disposal of the researcher and the acute and keen-minded skills of the pathologist. Notable among these pioneering efforts were the contributions of W. Ford Robertson, Santiago Ramon y Cajal, Pio del Rio-Hortega and Wilder Penfield amongst an entire cavalcade of other noteworthy figures. The term 'mesoglia' and 'third element of the nervous system' was bestowed upon these cells towards the beginning of the twentieth century to account for their separate origins from neurons and macroglia. It was later amended by del Rio-Hortega in 1919, to 'microglia' in order to further discriminate between true mesodermal elements and oligodendrocytes, previously regarded as a component of 'mesoglia'. This particular contention sparked much controversy among del Rio-Hortega's peers and resulted in an escalation of fruitful research throughout Europe that eventually declined up to the outbreak of the Second World War. The post-war years were a period of the 'dark ages' that cast doubt on the very existence and nature of microglia, until the 'renaissance' of research was once again rejuvenated in the 1960s, by a new cohort of intrigued minds: Cammermeyer, Blinzinger, Kreutzberg and others who saw in the 'third element' the potential that is now commonly ascribed to microglia: the intrinsic immune effector cells of the CNS. It is now universally accepted that microglia are involved as the first line of rapid defence in any pathology of the nervous system, and as such, present a diagnostic tool for the neuropathologist. Although our knowledge of microglia stems from an extensive body of work conducted over the last two decades, much of the earlier work (pre-1960s) has remained somewhat obscure. This is partly accountable due to the limited availability of translated works, and additionally to the lack of a compendium of these articles. This paper will present a comprehensive overview of the pioneering research on mononuclear phagocytes within the central nervous system, which has direct bearing on our present-day understanding of the concept of microglia.     

MESOGLIA & MICROGLIA – A Historical Review of the Concept of Mononuclear Phagocytes Within the Central Nervous System

More than a century and a half has elapsed since the first accounts of mesodermal phagocytic elements were proposed within the central nervous system. Over the intervening decades, body and substance were added to this concept through the advancement of histological techniques at the disposal of the researcher and the acute and keen-minded skills of the pathologist. Notable among these pioneering efforts were the contributions of W. Ford Robertson, Santiago Ramon y Cajal, Pio del Rio-Hortega and Wilder Penfield amongst an entire cavalcade of other noteworthy figures. The term ‘mesoglia’ and ‘third element of the nervous system’ was bestowed upon these cells towards the beginning of the twentieth century to account for their separate origins from neurons and macroglia. It was later amended by del Rio-Hortega in 1919, to ‘microglia’ in order to further discriminate between true mesodermal elements and oligodendrocytes, previously regarded as a component of ‘mesoglia’. This particular contention sparked much controversy among del Rio-Hortega’s peers and resulted in an escalation of fruitful research throughout Europe that eventually declined up to the outbreak of the Second World War. The post-war years were a period of the ‘dark ages’ that cast doubt on the very existence and nature of microglia, until the ‘renaissance’ of research was once again rejuvenated in the 1960s, by a new cohort of intrigued minds: Cammermeyer, Blinzinger, Kreutzberg and others who saw in the ‘third element’ the potential that is now commonly ascribed to microglia: the intrinsic immune effector cells of the CNS. It is now universally accepted that microglia are involved as the first line of rapid defence in any pathology of the nervous system, and as such, present a diagnostic tool for the neuropathologist. Although our knowledge of microglia stems from an extensive body of work conducted over the last two decades, much of the earlier work (pre-1960s) has remained somewhat obscure. This is partly accountable due to the limited availability of translated works, and additionally to the lack of a compendium of these articles. This paper will present a comprehensive overview of the pioneering research on mononuclear phagocytes within the central nervous system, which has direct bearing on our present-day understanding of the concept of microglia.     

The Central Institute for Brain Research in Amsterdam and its Directors

The Central Institute for Brain Research was founded in Amsterdam in 1908 as part of an international effort to study the nervous system with multiple institutions and various disciplines. The development of research in the past hundred years at the Brain Institute has hardly been documented. We analyze the history of this institute by means of brief portraits of its directors and their main research topics. It appears that each director introduced his own branch of neuroscience into the institute. Initially, mainly comparative neuroanatomical data were collected. Following the Second World War, the multidisciplinary approach slowly developed with research programs on systems neuroscience, neuroendocrinology, and brain disorders. Every new director introduced new approaches to the study of the brain and thus played an important role in keeping brain research in the Netherlands at the international forefront where it has been ever since its foundation in 1908.     

Origins of molecular neurobiology: the role of the physicists

The revolution in the foundations of physics at the beginning of the twentieth century suggested to several of its most prominent workers that biology was ripe for something similar. In consequence, a number of physicists moved into biology. They were highly influential in initiating a molecular biology in the 1950s. Two decades later it seemed to several of these migrants, and those they had influenced, that the major problems in molecular biology had been solved, and that it was time to move on to what seemed to them the final problem: the nervous system, consciousness, and the age-old mind-body problem. This paper reviews this "double migration" and shows how the hopes of the first generation of physicist-biologists were both realized and dashed. No new physical principles were discovered at work in the foundations of biology or neuroscience. On the other hand, the mind-set of those trained in physics proved immensely valuable in analyzing fundamental issues in both biology and neuroscience. It has been argued that the outcome of the molecular biology of the 1950s was a change in the concept of the gene from that of "a mysterious entity into that of a real molecular object" (Watson, 1965, p.6); the gates and channels which play such crucial roles in the functioning of nervous systems have been transformed in a similar way. Studies on highly simplified systems have also opened the prospect of finding the neural correlatives of numerous behaviors and neuropathologies. This increasing understanding at the molecular level is invaluable not only in devising rational therapies but also, by defining the material substrate of consciousness, in bringing the mind-body problem into sharper focus.     

Some aspects of the history of the law of dynamic polarization of the neuron. From William James to Sherrington, from Cajal and van Gehuchten to Golgi

William James was the first to suggest that propagation of impulses in the nervous system proceeds in one direction, from sensory to motor neurons, but not viceversa. His law of forward direction preceded the formulation of the law of dynamic polarization of van Gehuchten and Cajal, which assumed that nerve impulses are conducted cellulipetally along dendrites and cellulifugally along axons, based on different anatomo-functional properties of these neuronal components. Golgi did not accept the law of dynamic polarization because he believed that dendrites are involved in the nutrition of the neuron rather than in impulse propagation, and that impulses can travel in any direction in the axonal components of the diffuse nerve network. Sherrington in turn experimentally demonstrated that intraneuronic conduction is reversible, whereas, in accord with James's law, propagation of impulses along neuronal chains is irreversible, due to the valve-like action of synapses. The story of the law of dynamic polarization shows that neither Golgi nor Cajal paid much heed to Sherrington's findings and to neurophysiological studies in general, probably because they felt that histology alone could provide the key for understanding the general functioning of the nervous system. It is argued here that this attitude was detrimental to the progress of the neurosciences, because a multidisciplinary approach based on different techniques is inevitably called for in order to develop a plausible theory of the nervous system.     

Some Aspects of the History of the Law of Dynamic Polarization of the Neuron. From William James to Sherrington,from Cajal and Van Gehuchten to Golgi

William James was the first to suggest that propagation of impulses in the nervous system proceeds in one direction, from sensory to motor neurons, but not viceversa. His law of forward direction preceded the formulation of the law of dynamic polarization of van Gehuchten and Cajal, which assumed that nerve impulses are conducted cellulipetally along dendrites and cellulifugally along axons, based on different anatomo-functional properties of these neuronal components. Golgi did not accept the law of dynamic polarization because he believed that dendrites are involved in the nutrition of the neuron rather than in impulse propagation, and that impulses can travel in any direction in the axonal components of the diffuse nerve network. Sherrington in turn experimentally demonstrated that intraneuronic conduction is reversible, whereas, in accord with James's law, propagation of impulses along neuronal chains is irreversible, due to the valve-like action of synapses. The story of the law of dynamic polarization shows that neither Golgi nor Cajal paid much heed to Sherrington's findings and to neurophysiological studies in general, probably because they felt that histology alone could provide the key for understanding the general functioning of the nervous system. It is argued here that this attitude was detrimental to the progress of the neurosciences, because a multidisciplinary approach based on different techniques is inevitably called for in order to develop a plausible theory of the nervous system.     

White matter—Maximien Parchappe and the integration of articulate language

ABSTRACT

The Imperial Academy of Medicine of Paris met in the spring of 1865 to discuss the localization of speech. One of the participants was Maximien Parchappe (1800–1866), an alienist whose research interests lay in the cerebral cortex. This article addresses Maximien Parchappe’s concept that the cognitive elements of language—such as the translation of thoughts into words, the will to express them, and the means to do so—reside within the cortical gray matter, and that they are integrated through white-matter fibers. In so doing, Parchappe anticipated Carl Wernicke’s linking of the posterior aspects of the dominant frontal and temporal lobes in verbal expression, and Jules Dejerine’s linking of the angular gyrus and Wernicke’s area in the understanding of written language. Functional imaging has revived interest in language as a network of neuronal aggregates and has given new relevance to Parchappe’s concept of the functional organization of language.     

都市圈一体化研究进展与展望

一体化发展是区域高质量发展和协调治理的新要求,由于其空间尺度不同,出现了区域一体化、城市群一体化和都市圈一体化等多个概念。都市圈是城市群的重要组成单元和城镇化的重要空间载体,加强都市圈一体化研究,对于实现区域内部、区域与国家、区域与全球的协调融合发展具有重要意义。本文对近20年来中国都市圈一体化相关研究文献进行梳理。综述结果表明：(1)一体化及都市圈概念尚未形成统一的定义,使得都市圈一体化在概念表述上存在一定差异。(2)研究理论框架多借鉴经济学和管理学,理论的适配性限制了对都市圈一体化的机理研究。(3)多学科交叉融合研究匮乏,高适配性的理论体系构建还有待加强。(4)随着国家发展战略调整和区域一体化实践的深入,都市圈一体化研究正面临制度、功能、生态、文化和关系等方面的转向。     

Change and variability in Plio-Pleistocene climates: modelling the hominin response

Research into the links between climatic change and hominin evolution has generated numerous hypotheses. In recent years, methodological refinement of, and increased research effort directed towards, reliable proxies for palaeoclimatic change have provided a growing body of data with which to test such hypotheses. Whilst many archaeologists are aware of these data, few are cognizant of the wealth of techniques developed by theoretical biologists over the last half-century to explicitly address the evolutionary consequences of adaptation to temporally heterogeneous environments. The current paper expands and adapts one such technique for use with empirical data, and applies it to a global palaeoclimatic record spanning the last five million years, in order to discern the potential impact of environmental heterogeneity on hominin evolution during this period. Of particular interest are the contributions of climatic change, associated with directional selection, and climatic variability, associated with selection for phenotypic plasticity. At this macro-scale, results suggest an early peak in selection for plasticity at approximately 2–2.7 mya, combined with three major shifts in directional selection at approximately 3.3–3.4, 1.4–1.5, and 0.5–0.6 mya. These results are employed to relate the fossil and archaeological records to a number of environmental hypotheses of human evolution. In particular, it is argued that the origins of the genus Homo and the spread of Oldowan technology are associated not with a major turnover pulse, but with a period of selection for phenotypic plasticity.     

The impossible interview with the man of the neuron doctrine. Interview by Edward G Jones

This paper follows the form of that by Mazzarello that precedes it (Mazzarello, 2006) and presents an imaginary interview with Santiago Ramón y Cajal in December 1906. A few days earlier Cajal had been awarded the Nobel Prize for Physiology or Medicine, an award that he shared equally with Professor Camillo Golgi. Golgi had been recognized for his work as a pioneer into investigations of the nervous system, primarily on account of his discovery of the "black reaction" of silver chromate impregnation of whole nerve cells and their processes. Cajal had been recognized for his implementation of that method and for laying with it the foundations of what was to become modern neuroanatomical science. Paradoxically, the two awardees had been led by their researches to diametrically opposed views of the organization of the nervous system. Golgi believed in a continuous network of axons that formed the basis of all the integrative properties of the nervous system, while Cajal had provided the information that led to the formulation of the neuron doctrine that saw the nervous system as being made up of chains of discontinuous cells joined by polarized functional contacts that we now call synapses. The paper takes the form of an interview with Professor Cajal in the Grand Hotel Stockholm. His responses to questions posed by the imaginary interviewer are all taken from Cajal's own writings.     

Louis Ranvier (1835-1922): the contribution of microscopy to physiology and the renewal of French general anatomy

The French neurohistologist Louis-Antoine Ranvier (1835-1922), somewhat neglected in classical histories of nineteenth-century studies on the nervous system, developed a personal style, traditionally referred to as a synthesis between histology and physiology. Ranvier's research was not centered on the brain. Rather, he remained attached to the intimate nature of minute structures, with a style marked by the concept of generality. Ranvier's original style and role in the development of French histology and anatomie générale are analyzed, and their significance evaluated. Ranvier is reassessed as a prominent figure and as the leader in the renewal of the French anatomy.     

Henry Herbert Donaldson’s (1857–1938) contribution to an organized approach to the experimental study of the mammalian central nervous system

ABSTRACT

This article shows that the academic and research careers of Henry Herbert Donaldson (1857–1938) were directed to provide basic information about the growth of the vertebrate nervous system and to provide standards and the means to make such research efficient. He earned the reputation of making the albino rat a standard laboratory animal. His academic career began when he was an undergraduate at Yale University in 1875 and concluded with his death as Professor and Head of the Department of Neurology at the Wistar Institute of Anatomy and Biology of the University of Pennsylvania in 1938. During that period, pivotal experiences occurred, including research in physiological chemistry with Chittenden at the Sheffield School at Yale, graduate study at Johns Hopkins University, postgraduate study in Europe, and professorial positions at Clark University and the University of Chicago. It was at Johns Hopkins University that Donaldson learned about the need for physiological, anatomical, and psychophysical research and about the techniques to allow such research. It was at Clark University that he had first-hand and detailed experience with the anatomy of the brain of a deaf-blind-mute woman, as he attempted to correlate her sensory deficits with her brain development. It was at Clark University that he clearly recognized the need for standardization in neurological research. At the University of Chicago, he developed administrative skills and began a coordinated research effort to delimit the growth of the nervous system. It was at Chicago that he learned that the albino rat could be a reasonable subject for such research. It was also at Chicago that he was able to formulate ideas about the future organizational needs of human neuroanatomy. It was at the Wistar Institute that his research program and his professional career matured. He organized a research effort to elucidate the growth of the nervous system. He contributed to the coordination of neurological research in the United States and Europe. It was while at the Wistar Institute that he became well-known for making the albino rat a standard laboratory mammal—a convenient living material for research.     

区域人地关系定量研究

首先评述了目前人地关系研究概况,指出这些研究成果多缺乏具体的可操作措施,界定了人地关系的内涵和研究内容,接着从自然村域的角度设计了区域人地关系的定量研究思路,包括人地关系内部作用机理、单村研究、多村比较研究及不同空间尺度研究的推绎等,最后指出区域人地关系定量研究应结合有关技术     

Rethinking Overdetermination, Structural Power, and Social Change: A Critique of Gibson-Graham, Resnick, and Wolff

Working in the wake of theoretical tendencies that became prominent within geography during the 1980s, many studies of resistance have either bracketed or ignored structural power, with some versions of poststructuralism simply denying that structural power is a useful concept in a world where power is putatively highly fluid and dispersed. These sorts of approaches, exemplified by the recent works of J K Gibson-Graham, Stephen A Resnick, and Richard D Wolff (GGRW), limit the ability of studies of resistance to articulate the conditions under which political and social struggles might transcend resistance and succeed in liberating groups of humans from the oppressive conditions against which they struggle. In this paper, I discuss issues surrounding analysis of structural power in the wake of poststructuralist critiques of "structural Marxism," presenting an alternative to GGRW's interpretation of Louis Althusser's concept of "overdetermination." Overdetermination is a crucial concept, because it is rightly seen as the key to a noneconomistic Marxism and has been championed as such by GGRW. I re-examine the roots of Althusser's concept in the writings of Lenin and Mao, arguing for a way of reading overdetermination that is both noneconomistic and compatible with a notion of structural power.