Brain Research Reviews最新文献

An overview of current concepts on neuroinflammation and on the dialogue between neurons and non-neuronal cells in three important infections of the central nervous systems (rabies, cerebral malaria, and human African trypanosomiasis or sleeping sickness) is here presented. Large numbers of cases affected by these diseases are currently reported. In the context of an issue dedicated to Camillo Golgi, historical notes on seminal discoveries on these diseases are also presented. Neuroinflammation is currently closely associated with pathogenetic mechanisms of chronic neurodegenerative diseases. Neuroinflammatory signaling in brain infections is instead relatively neglected in the neuroscience community, despite the fact that the above infections provide paradigmatic examples of alterations of the intercellular crosstalk between neurons and non-neuronal cells. In rabies, strategies of immune evasion of the host lead to silencing neuroinflammatory signaling. In the intravascular pathology which characterizes cerebral malaria, leukocytes and Plasmodium do not enter the brain parenchyma. In sleeping sickness, leukocytes and African trypanosomes invade the brain parenchyma at an advanced stage of infection. Both the latter pathologies leave open many questions on the targeting of neuronal functions and on the pathogenetic role of non-neuronal cells, and in particular astrocytes and microglia, in these diseases. All three infections are hallmarked by very severe clinical pictures and relative sparing of neuronal structure. Multidisciplinary approaches and a concerted action of the neuroscience community are needed to shed light on intercellular crosstalk in these dreadful brain diseases. Such effort could also lead to new knowledge on non-neuronal mechanisms which determine neuronal death or survival.

ATP accomplishes important roles in brain, where it functions as neurotransmitter or co-transmitter, being stored and released either as single mediator or together with other neuromodulators. In the last years, the purinergic system has emerged as the most relevant mechanism for intercellular signalling in the nervous system, affecting communication between many types of neurons and all types of glia. In this review, we will focus on recently reported data which describe the role of ATP in bidirectional signalling between neurons and different populations of glial cells, in both peripheral and central system.

The name of Camillo Golgi is inextricably associated, in the mind of most neuroscientists, with the theory that nerve cells communicate with one another by means of an intricate network of anastomosing axonal branches contained in the neuropil intervening between cell bodies in the gray matter of the brain and spinal cord. Examination, however, of Golgi's drawings in the papers published in the decade intervening between publication of his method (1873) and the beginning of his studies on malaria (1885) shows that axonal arborization in the cerebellar cortex and olfactory bulb are depicted as independent of one other. This is in striking contrast with the drawings included by Golgi in his 1906 Nobel lecture where the entire granular layer of the cerebellar cortex is occupied by a network of branching and anastomosing nerve processes. Thus, Golgi in his original papers on the cerebellum represents nerve cells as discrete units and only later in life merges axonal arborizations in the context of a lecture in defense of the reticular theory.

In recognition of the impact that a powerful new anatomical tool, such as the Golgi method, can have, this essay highlights the enormous influence that biocytin-filling has had on modern neuroscience. This method has allowed neurones that have been recorded intracellularly, ‘whole-cell’ or juxta-cellularly, to be identified anatomically, forming a vital link between functional and structural studies. It has been applied throughout the nervous system and has become a fundamental component of our technical armoury. A comprehensive survey of the applications to which the biocytin-filling approach has been put, would fill a large volume. This essay therefore focusses on one area, neocortical microcircuitry and the ways in which combining physiology and anatomy have revealed rules that help us explain its previously indecipherable variability and complexity.

With the growing realization in the 1930s that the brain played a crucial role in regulating the secretions of the pituitary gland, neuroendocrinology as we now know it developed from two rather separate directions. One approach relied heavily on morphological techniques to define neurosecretion; a novel, but for many years flawed model that was originally developed to explain the presence of gland-like cells in the diencephalon. During its first 20 years neurosecretion, as a concept, made no significant contribution to our understanding of how the pituitary was controlled. Then, following the identification by Sanford Palay and Wolfgang Bargmann of a continuous neurosecretory pathway from the hypothalamus to the neural lobe, neurosecretion became incorporated into a more broadly based concept of pituitary function, particularly regarding the neural lobe. The second approach integrated structural and functional methods to investigate neural regulation of the pituitary. This work eventually explained how the pituitary was controlled by the brain. It led directly to our understanding of the control of vasopressin and oxytocin release by neuroendocrine terminals in the neural lobe, the neurohumoral control of the pars distalis, and eventually to a detailed description of the neural networks that control pituitary function. As increasingly sophisticated morphological, neurophysiological, and eventually molecular biological techniques were applied to the problem, the original notion of the diencephalic gland and neurosecretion became unsustainable. The gland-nerve cells of the 1930s became the neurosecretory cells of the 1940s and 1950s, and then finally neuroendocrine neurons in the 1960s. From then on neuroendocrinology developed into the more unified discipline we know today. The chronology of these two approaches will be examined here using examples from research that occurred approximately between 1920 and 1965. The goal is not to give a comprehensive history of pituitary function or neuroendocrinology. Instead, the focus will be to compare the rationales and effectiveness of two contrasting experimental approaches: predominantly structural analyses as opposed to more integrated approaches.

Camillo Golgi and Santiago Ramón y Cajal were the two main investigators that revealed the morphological organization of the cerebellar cortex, although they never shared the same basic concepts. While for Golgi all axons fused into a large syncytium (the diffuse nerve network), for Cajal they had free endings and communication between neurons was done by contiguity not by continuity. The classical diagrammatic representation of the cerebellar circuitry shown by Cajal in his Croonian lecture (1894), although still valid, has drastically change by the accumulation of the great amount of data generated from 1894 to our days. The topic of this review is to briefly summarize this new knowledge, and to confront it with Cajal's concepts, to determine whether or not the added complexity to the circuit invalidates the Cajal's principles. Our conclusion is that although most of these principles are consolidated, the applicability of the law of dynamic polarization does not adapt to some of them.

The mechanisms underlying the production of thoughts by exceedingly complex cellular networks that construct the human brain constitute the most challenging problem of natural sciences. Our understanding of the brain function is very much shaped by the neuronal doctrine that assumes that neuronal networks represent the only substrate for cognition. These neuronal networks however are embedded into much larger and probably more complex network formed by neuroglia. The latter, although being electrically silent, employ many different mechanisms for intercellular signalling. It appears that astrocytes can control synaptic networks and in such a capacity they may represent an integral component of the computational power of the brain rather than being just brain “connective tissue”. The fundamental question of whether neuroglia is involved in cognition and information processing remains, however, open. Indeed, a remarkable increase in the number of glial cells that distinguishes the human brain can be simply a result of exceedingly high specialisation of the neuronal networks, which delegated all matters of survival and maintenance to the neuroglia. At the same time potential power of analogue processing offered by internally connected glial networks may represent the alternative mechanism involved in cognition.