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| Equipment of the laboratory of Camillo Golgi in the years that followed his appointment as Professor of Histology at the University of Pavia in 1876, when Golgi's studies focused on the nervous system. The equipment is on display at the Golgi museum (Berzero et al., 2018). (A) Microtome by the German anatomist and physiologist Gustav Fritsch (1838-1927), bought in 1878. (B) Microtome by the French histologist and anatomist Louis Ranvier (1835-1922) to cut by hand, with the razor shown in the figure, sections sufficiently thin for microscopic examination from tissue blocks fixed to the cylinder; this microtome was bought in 1879. (C) Hartnack-Prazmowski microscope, bought in 1877 from the firm Hartnack had established in Paris in partnership with the Polish mathematician and astronomer Adam Prazmowski (1821-1885). (D) Microscope by Edmund Hartnack (1826-1891), renowned German microscope maker, bought in 1876.
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The metallic impregnation invented by Camillo Golgi in 1873 has allowed the visualization of individual neurons in their entirety, leading to a breakthrough in the knowledge on the structure of the nervous system. Professor of Histology and of General Pathology, Golgi worked for decades at the University of Pavia, leading a very active laboratory....
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Citations
... In 1873, Camillo Golgi developed the non-transgenic single cell-labeling Golgi staining method [1], which enabled the sparse and random visualization of the morphology of single neurons. For more than 100 years, Golgi staining has been a standard method for dissecting the morphological structures of neurons and neuronal networks [1][2][3]. ...
... In 1873, Camillo Golgi developed the non-transgenic single cell-labeling Golgi staining method [1], which enabled the sparse and random visualization of the morphology of single neurons. For more than 100 years, Golgi staining has been a standard method for dissecting the morphological structures of neurons and neuronal networks [1][2][3]. Although Golgi staining is a non-transgenic method, it is one of the seminal methods in the history of life science. ...
Simple Summary
The neuronal circuits are essential for memory, recognition, and behavior but are too complex to be examined with ordinary, global labeling methods. Moreover, the role of each protein/gene in forming circuits is one of the biggest open questions in modern biology. Single-cell labeling methods are potent approaches for examining neuronal structure and circuits. Single-cell transgenic methods also enable single-cell gene knockout and modulation of neuronal activity, which can reveal their functional roles. This review summarizes the details of single neuronal labeling methods of non-transgenic and transgenic strategies and their contributions to our understanding of neuronal structures and functions.
Abstract
The brain network consists of ten billion neurons and is the most complex structure in the universe. Understanding the structure of complex brain networks and neuronal functions is one of the main goals of modern neuroscience. Since the seminal invention of Golgi staining, single-cell labeling methods have been among the most potent approaches for dissecting neuronal structures and neural circuits. Furthermore, the development of sparse single-cell transgenic methods has enabled single-cell gene knockout studies to examine the local functions of various genes in neural circuits and synapses. Here, we review non-transgenic single-cell labeling methods and recent advances in transgenic strategies for sparse single neuronal labeling. These methods and strategies will fundamentally contribute to the understanding of brain structure and function.
... El gancho experimental inicial vino dado por la invención, por parte del histólogo italiano Camillo Golgi, del método de tinción del tejido nervioso basado en el nitrato de plata, la reazzione nera o reacción negra. Varios historiadores de la ciencia lo llaman un "método revolucionario" (Cimino 1999;Shepherd 2015;Bentivoglio et al. 2019). Por mecanismos todavía desconocidos, el método permite visualizar selectivamente, en color negro, los cuerpos celulares, dendritas y axones de algunas pocas células por pieza, sobre un trasfondo de color amarillo. ...
El papel determinante que desempeña la innovación técnica en el progreso neurocientífico plantea desafíos especiales a la filosofía del cambio científico de raigambre kuhniana. Algunos filósofos de la neurociencia sostienen que las revoluciones en neurociencia no involucran cambios de paradigma, sino que dependen exclusivamente de la innovación técnica o experimental. Mediante el estudio del episodio histórico del descubrimiento de la neurona (1873-1909), argumento que las revoluciones en neurociencia, como muchas otras revoluciones de laboratorio, están frecuentemente impulsadas por el entrelazamiento de innovaciones técnicas y cambio conceptual.
... This is very useful, especially for studying the histology of the nervous system, as it allowed Golgi to easily differentiate axons from dendrites. Unlike the classical methods, the fixation by using solutions with metals determines the preferential precipitation on certain structures, through a mechanism that is not even to this day completely elucidated [7]. ...
... Cajal was amazed by the quality of Camillo Golgi's tissues impregnated using the Black Reaction method, and in fact, more than half of his sketches were made using this method. Moreover, Cajal even made certain improvements to the protocol [7]. Thus, in 1891, "The Neural Theory" was formulated by the Spanish researcher, a theory which denounces The Reticular Theory as being obsolete. ...
Camillo Golgi (Figure 1) is one of the most prestigious personalities of modern medicine [...]
... Experimental techniques used to investigate neurotransmission have evolved considerably over the last century (Sotelo, 2008;VoŽeh, 2015;Cavero et al., 2017;Bentivoglio et al., 2019). The extensive application of 3D morphological reconstructions (Guo et al., 2022), immunochemistry, patch-clamp recordings, calcium imaging, genomics, and proteomics has allowed the creation of atlases, such as the Allen Brain Atlas (Gilbert, 2018), which summarizes the knowledge about brain neurons and circuits along with the distribution of synaptic receptors and molecules, both in rodents and humans. ...
The neuroscientific field benefits from the conjoint evolution of experimental and computational techniques, allowing for the reconstruction and simulation of complex models of neurons and synapses. Chemical synapses are characterized by presynaptic vesicle cycling, neurotransmitter diffusion, and postsynaptic receptor activation, which eventually lead to postsynaptic currents and subsequent membrane potential changes. These mechanisms have been accurately modeled for different synapses and receptor types (AMPA, NMDA, and GABA) of the cerebellar cortical network, allowing simulation of their impact on computation. Of special relevance is short-term synaptic plasticity, which generates spatiotemporal filtering in local microcircuits and controls burst transmission and information flow through the network. Here, we present how data-driven computational models recapitulate the properties of neurotransmission at cerebellar synapses. The simulation of microcircuit models is starting to reveal how diverse synaptic mechanisms shape the spatiotemporal profiles of circuit activity and computation.
... We could also gain a sense of a student's baseline level of conceptualization of the nervous system by evaluating drawings of their work in class before and after they have received training, as has been performed in other courses for assessment or evaluation [88,89]. As has been noted by others [90,91], the addition to our curriculum of materials that emphasize the history of the histological processing of brain tissue and atlas-mapping/drawing techniques could further enhance student appreciation of the research and discovery process [e.g., [92,93]]. ...
Recent efforts to reform postsecondary STEM education in the U.S. have resulted in the creation of course-based undergraduate research experiences (CUREs), which, among other outcomes, have successfully retained freshmen in their chosen STEM majors and provided them with a greater sense of identity as scientists by enabling them to experience how research is conducted in a laboratory setting. In 2014, we launched our own laboratory-based CURE, Brain Mapping & Connectomics (BMC). Now in its seventh year, BMC trains University of Texas at El Paso (UTEP) undergraduates to identify and label neuron populations in the rat brain, analyze their cytoarchitecture, and draw their detailed chemoarchitecture onto standardized rat brain atlas maps in stereotaxic space. Significantly, some BMC students produce atlas drawings derived from their coursework or from further independent study after the course that are being presented and/or published in the scientific literature. These maps should prove useful to neuroscientists seeking to experimentally target elusive neuron populations. Here, we review the procedures taught in BMC that have empowered students to learn about the scientific process. We contextualize our efforts with those similarly carried out over a century ago to reform U.S. medical education. Notably, we have uncovered historical records that highlight interesting resonances between our curriculum and that created at the Johns Hopkins University Medical School (JHUMS) in the 1890s. Although the two programs are over a century apart and were created for students of differing career levels, many aspects between them are strikingly similar, including the unique atlas-based brain mapping methods they encouraged students to learn. A notable example of these efforts was the brain atlas maps published by Florence Sabin, a JHUMS student who later became the first woman to be elected to the U.S. National Academy of Sciences. We conclude by discussing how the revitalization of century-old methods and their dissemination to the next generation of scientists in BMC not only provides student benefit and academic development, but also acts to preserve what are increasingly becoming “lost arts” critical for advancing neuroscience – brain histology, cytoarchitectonics, and atlas-based mapping of novel brain structure.
... After years of improvement, the consumption time of Golgi staining has been significantly reduced, and the imaging quality has been increased Mallick 2010, 2012;Narayanan et al. 2020;Czechowska et al. 2019). However, we find that the GCM still has several shortcomings, such as high background staining, artefacts, and incomplete vasculature labelling (Mizutani et al. 2008;Bentivoglio et al. 2019;Rosoklija et al. 2014). Our study optimized it in spinal cord presentation. ...
Exploring the three-dimensional (3D) morphology of neurons is essential to understanding spinal cord function and associated diseases comprehensively. However, 3D imaging of the neuronal network in the broad region of the spinal cord at cellular resolution remains a challenge in the field of neuroscience. In this study, to obtain high-resolution 3D imaging of a detailed neuronal network in the mass of the spinal cord, the combination of synchrotron radiation micro-computed tomography (SRμCT) and the Golgi-cox staining were used. We optimized the Golgi-Cox method (GCM) and developed a modified GCM (M-GCM), which improved background staining, reduced the number of artefacts, and diminished the impact of incomplete vasculature compared to the current GCM. Moreover, we achieved high-resolution 3D imaging of the detailed neuronal network in the spinal cord through the combination of SRμCT and M-GCM. Our results showed that the M-GCM increased the contrast between the neuronal structure and its surrounding extracellular matrix. Compared to the GCM, the M-GCM also diminished the impact of the artefacts and incomplete vasculature on the 3D image. Additionally, the 3D neuronal architecture was successfully quantified using a combination of SRμCT and M-GCM. The SRμCT was shown to be a valuable non-destructive tool for 3D visualization of the neuronal network in the broad 3D region of the spinal cord. Such a combinatorial method will, therefore, transform the presentation of Golgi staining from 2 to 3D, providing significant improvements in the 3D rendering of the neuronal network.
... The cerebellar Golgi cell [1][2][3] is the principal inhibitory interneuron of the cerebellar granular layer [4] and is supposed to play a critical role for spatio-temporal reconfiguration of incoming inputs by regulating neurotransmission and synaptic plasticity along the mossy fiber-granule cell pathway [5][6][7]. Golgi cells are wired in feed-forward and feed-back loops with granule cells and form a functional syncytium through gap junctions [8]. ...
The Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. Although recent works have highlighted the complexity of their dendritic organization and synaptic inputs, the mechanisms through which these neurons integrate complex input patterns remained unknown. Here we have used 8 detailed morphological reconstructions to develop multicompartmental models of Golgi cells, in which Na, Ca, and K channels were distributed along dendrites, soma, axonal initial segment and axon. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons. Basal dendrites turned out to be more tightly electrically coupled to the axon initial segment than apical dendrites. During synaptic transmission, parallel fibers caused slow Ca-dependent depolarizations in apical dendrites that boosted the axon initial segment encoder and Na-spike backpropagation into basal dendrites, while inhibitory synapses effectively shunted backpropagating currents. This oriented dendritic processing set up a coincidence detector controlling voltage-dependent NMDA receptor unblock in basal dendrites, which, by regulating local calcium influx, may provide the basis for spike-timing dependent plasticity anticipated by theory.
... This work collects the results of many researches on Camillo Golgi and his school that I published in the last thirty years. In particular I refer toMazzarello 2002;2010;2011;2018;2019;Mazzarello and Bentivoglio 1998;Mazzarello et al. 2001;Mazzarello et al. 2003;Mazzarello et al. 2004;Mazzarello et al. 2006;Mazzarello et al. 2009;Galliano et al. 2010;Raviola and Mazzarello 2011;Shepherd et al. 2011;Bentivoglio et al. 2019. ...
This article outlines the fundamental phases of the scientific life of Camillo Golgi, the first Ital-ian to win a Nobel Prize and one of the protagonists of European biomedical research between the 19th and 20th centuries. In August 1873 a thirty-year-old Lombard medical doctor, Camillo Golgi, published in the journal Gazzetta Medica Italiana-Lombardia a brief note from the modest title Sulla struttura della sostanza grigia del cervello ("On the structure of the grey substance of the brain"). The paper gave a hasty description of a new histological procedure for the study of the microscopic morphological structure of the central nervous system. It also provided a quick account of some substantial scientific novelties that the method had allowed to obtain. Making the silver nitrate act on pieces of brain previously hardened with potassium dichromate in succession, Golgi had succeeded in realizing the dream of all the histologists who had previously posed the problem of clarifying the spatial disposition and the remote projections of the cellular elements of which the central nervous system is composed. The miraculous and mysterious contact between the potassium dichromate and the silver nitrate, in fact, determined the precipitation of a brown salt (the silver chromate) that, in a completely unexpected and unpredictable way, occupied the body of the cell and all its extensions , up to the most remote distances. But what most impressed was the random-ness of the reaction: only a minority of the cellular elements, present in the microscopic field, were stained in black. At first sight what could have been considered a partiality (and therefore a defect) of the method, was instead his great strength. The cells, and their projections, clearly emerged with respect to the surrounding structures , thus creating almost a "microdissection" of the single elements that were like "extracted" from the tangled neurocytological interweaving within which they were 1 This work collects the results of many researches on Camillo Golgi and his school that I published in the last thirty years.
We are approximately 34 trillion cells under direct or indirect control by 80 billion neurons connected in functional units. To interact with our environment, we need to process enormous amounts of sensory information and make decisions before executing complex behaviors. Most of the time we are unaware of the cellular machinery that must be brought to task. This article discusses the main classes of cells and the suite of cellular processes that allow spatial and temporal processing of information in the nervous system.
