Olov Oscarsson (1931-1996) of Lund University, a Pioneer in Cerebellar Neurobiology.

The present Cerebellar Classic highlights the experimental work of the Swedish neurophysiologist Olov Oscarsson (1931-1996) on the afferent innervation of the cerebellum by axons emanating from neurons in the spinal cord and the inferior olive. Historically, the schemes of cerebellar division had been principally based on the external morphology of lobules and fissures. However, the macroscopic anatomical division of the cerebellum does not coincide with its pattern of functional organization. By defining a system of longitudinal somatotopy, Oscarsson contributed to the much needed plan of cerebellar division that correlates experimental information on axonal connections with physiology. His contribution has ultimately led to the currently accepted microzonal modular scheme of cerebellar corticonuclear microcomplexes.

Neurobiological and pathophysiological concepts of Christfried Jakob (1866-1956) on language and aphasia: An English translation of two communications [1910,1932] and a modern perspective.

The aim of the present article is to preserve, in English translation, two historical communications on aphasia and the pathophysiology of language by the neurobiologist Christfried Jakob (1866-1956) of Buenos Aires, and to place them in a modern perspective. The morphofunctional basis of human language and its pathology occupied Jakob's mind over three decades. His synthetic conclusions were based on the neuropathological examination of dozens of aphasic cases from the Hospital de Las Mercedes and the National Women's Psychiatric Hospital between 1906 and 1936. Special mention is made of the role of the cerebellum, the thalamus, and their connections with the cerebral cortex, and the language network. Current research and imaging studies support and elaborate that which Jacob presented so many years ago; many of his analyses and ideas are informative and remain relevant today.

Paraneoplastic Ataxia: Antibodies at the Forefront Have Become Routine Biomarkers.

Paraneoplastic cerebellopathies are immune-mediated disorders targeting primarily the cerebellar circuitry, often presenting in a subacute course. The syndrome often develops before the cancer. Therefore, its identification often leads secondarily to a diagnosis of cancer, a critical step to stabilize symptoms. Two categories of antibodies have been identified these last 30 years: (a) onconeuronal antibodies which are directed against intracellular antigens, and (b) antibodies which are directed against synaptic and cell surface proteins. These latter impact on the location and function of the antigens, causing a genuine neuronal dysfunction. Appropriate and fast tumor screening has emerged as a recommendation facing a subacute cerebellar syndrome suspected to be paraneoplastic. Search for antibodies is now a milestone for the diagnosis.

Nothnagel Syndrome.

The internist Hermann Nothnagel (1841-1905) took a special interest in the cerebellum. In an early experimental study on rabbits conducted in 1876, he demonstrated the involvement of the vermis in the pathophysiology of motor ataxia. Between 1879 and 1889, he reported four cases of tectal tumors that clinically manifested with bilateral ophthalmoplegia and unilateral gait ataxia, culminating in the Cerebellar Classic highlighted here. Nothnagel attributed this clinical syndrome to lesions of the colliculi ("quadrigeminal bodies") and compression of the nuclei of the third cranial nerves, but also left open the possibility of the involvement of neighboring structures, such as the cerebellar vermis. Today, the ataxic component of Nothnagel syndrome is explained by a dorsal midbrain abnormality of either neoplastic or vascular origin, involving the superior cerebellar peduncles, besides the oculomotor nerves.

Hernias of the Cerebellum.

The present Cerebellar Classic highlights a paper published in 1908 by the American pathologist Simeon Burt Wolbach (1880-1954), in which he reported multiple hernias of the cerebellum for the first time in 9 cases of increased intracranial pressure. The importance of the meninges and the anatomy of involved compartments is emphasized.

The Pioneer Neuropharmacologist Alfred Fröhlich (1871-1953) and the Origins of Neuroendocrinology: A Sesquicentennial Remembrance.

The birth of neuroendocrinology as a scientific discipline is traced back to 1900-1901, when Joseph Babinski, Alfred Fröhlich, and Harvey Cushing independently identified adiposogenital dystrophy (Fröhlich syndrome), and related gonadal underdevelopment and obesity to a tumor near the pituitary gland. This discovery prompted decades of research into the brain mechanisms responsible for the control of peripheral metabolism and endocrine functions. On the occasion of the 150th anniversary of Fröhlich's birth, this study traces the origins of his intellectual formation and his association with renowned contemporaries in Austria, England, Italy, and finally Cincinnati, Ohio, where he sought refuge after Austria's annexation by Nazi Germany. Fröhlich interacted with seminal figures in biomedicine, including Lothar von Frankl-Hochwart, Hans Horst Meyer, Ernst Peter Pick, Harvey Cushing, John Newport Langley, and the Nobel laureates Charles Scott Sherrington and Otto Loewi. Alfred Fröhlich, one of the 20th century's most emblematic physicians, left his mark on neurophysiology and neuropharmacology with important works, and published authoritative manuals of drug dispensing and clinical therapy. He confronted the calamities of two World Wars with remarkable resilience like many of his Viennese colleagues who, overcoming the constraints of National Socialism, settled overseas to fulfil their calling as physicians, researchers, and teachers.

The Discovery of the Monoaminergic Innervation of the Cerebellum: Convergence of Divergent and Point-to-Point Systems.

This Cerebellar Classic highlights the landmark discovery of the innervation of the cerebellar cortex and cerebellar nuclei by noradrenergic and serotoninergic axons emanating, respectively, from the locus coeruleus and the raphé nuclei. Since then, modulation of the activity of cerebellar neurons by the monoamine systems has been studied extensively, as well as their reorganization and modifications during development, plasticity, and disease. The discovery of noradrenergic and serotoninergic innervation of the cerebellum has been a crucial step in understanding the neurochemical relationships between brainstem nuclei and the cerebellum, and the attempts to treat cerebellar ataxias pharmacologically. The large neurochemical repertoire of the cerebellum represents one of the complexities and challenges in the modern appraisal of cerebellar disorders.

Postnatal Neurogenesis Beyond Rodents: the Groundbreaking Research of Joseph Altman and Gopal Das.

An integral component of neural ontogeny and plasticity is the ongoing generation of new neurons from precursor cells throughout the lifespan in virtually all animals with a nervous system. In mammals, postnatal neurogenesis has been documented in the cerebellum, olfactory bulb, hippocampus, striatum, substantia nigra, hypothalamus, and amygdala. Germinal centers of new neuron production in the adult brain have been identified in the neuroepithelium of the subventricular zone and the dentate gyrus. One of the earliest lines of evidence gathered came from studies on the production of cerebellar microneurons in the external germinal layer of rodents and carnivores in the 1960s and 1970s. The undeniable pioneer of that research was the insightful developmental neurobiologist Joseph Altman (1925-2016). This Cerebellar Classic is devoted to the groundbreaking work of Altman and his graduate student and, subsequently, fellow faculty member, Gopal Das (1933-1991), on postnatal neurogenesis using tritiated thymidine autoradiography to tag newly formed neurons in the cerebellum of cats. Perseverant to their ideas and patiently working in West Lafayette (Indiana), they were the founders of two fields that brought about paradigm shifts and led to an explosive growth in brain research: adult neurogenesis and neural tissue transplantation.

"A Great Reinforcing Organ": the Cerebellum According to Silas Weir Mitchell.

This Cerebellar Classic highlights a work by the physician and novelist, Silas Weir Mitchell (1829-1914), a pupil of Claude Bernard and a founding father of American neurology. Published in the aftermath of the American Civil War, the article reported observations on cerebellar physiology based on ablation and tissue freezing experiments in pigeons, rabbits, and guinea pigs. Mitchell communicated his results before the Academy of Natural Sciences of Philadelphia, and proposed a general theory of the cerebellum as an augmenting and reinforcing organ to the cerebrospinal motor system. After reviewing and contrasting previous theories of Flourens and Bouillaud, Mitchell formulated his own theory, which was in line with the views of Rolando and Luys. The theory emphasized the necessity, initially suggested by Brown-Séquard, of distinguishing between phenomena due to loss of function and those due to irritation as a central principle that should guide any physiological research.