It was necessary to wait the “germ theory of disease” of Louis Pasteur (1829–1895) and its application in clinical medicine, initially by Joseph Lister (1827–1912), with the use of carbolic acid as an antiseptic, and subsequently by Lawson Tait (1845–1899) and Ernst von Bergmann (1836–1907) which went from antisepsis to asepsis. These medical advances have allowed Luigi Luciani (1840–1919), in that period professor of physiology at the University of Florence, to publish in 1891 [8] his observations on a dog survived the cerebellectomy, with the description of a triad of symptoms (asthenia, atony and astasis), unquestionably of cerebellar origin, that confirmed the intuition of Flourens. In the same years (1894), Spanish neuroscientist and future Nobel laureate Santiago Ramón y Cajal (1852–1934) published what is considered the first modern textbook of neuroanatomy [9], with a clear depiction of the cerebellar cortex (Fig. 5).

Fig. 5 Drawing of Purkinje cells (a) and granule cells (b) from pigeon cerebellum by Santiago Ramón y Cajal. Instituto Santiago Ramón y Cajal, Madrid, Spain Full size image

The first systematic description of the symptoms of cerebellar lesions in man was carried out by the British neurologist Gordon Morgan Holmes (1876 –1965). During World War I he was neurologist with the British Expeditionary Forces and working in a field hospital he had the opportunity to investigate the effects of traumatic lesions involving the cerebellum. In 1922 Holmes’ observations on patients with cerebellar wounds as well as tumors were published in his Croonian Lectures to the Royal College of Physicians [10].

The general conclusion reached before World War II was that the main role of the cerebellum is to detail the different aspects of a movement, not to initiate movements or to decide which movements to execute. After the war, there was a significant increase in knowledge of circuitry and electrophysiology of the cerebellum, summarized in 1967 in a book, The Cerebellum as a Neuronal Machine [11], written by the Nobel laureate John C. Eccles (1903–1997), Japanese neuroscientist Masao Ito, and Hungarian anatomist János Szentágothai (1912–1994), followed in 1974 by a review, Cerebrocerebellar communication systems [12], written by two neurophysiologists, the American Gary I. Allen and the Japanese Nakaakira Tsukahara (1933–1985).

In the same years it was suggested that the cerebellum is involved in motor learning. Most theories that attempt to explain the role of cerebellar circuits in motor learning are derived from the ideas of British neuroscientist and psychologist David C. Marr (1945–1980) and of American engineer James S. Albus (1935–2011). Both attributed an important role to climbing fiber activity capable to cause synchronously activated parallel fiber inputs, to be strengthened for Marr [13] and to be weakened for Albus [14]. In the 1980s, the discovery in the cerebellum of Long Term Depression (LTD) was considered as a form of synaptic plasticity involved in motor learning. LTD occurs when impulses of a set of granule cells and one climbing fiber reach the same Purkinje cell synchronously and repeatedly; synaptic transmission from the granule cells to the Purkinje cell is then persistently depressed [15]. Although LTD is now well characterized, its contribution to motor learning remain controversial [16].

Up to the 1990s the cerebellum was almost universally believed to be primarily involved in movement, but latest results have led to consider that view too restrictive. Imaging studies have allowed to detect cerebellar activation in relation to cognitive activities and numerous correlations between the cerebellum and non-motor regions of the cerebral cortex were highlighted. Moreover, in patients with lesions restricted to the cerebellum, non-motor symptoms have been frequently recognized. In 1998, the American neurologist Jeremy D. Schmahmann [17] described the Cerebellar Cognitive Affective Syndrome, characterized by impairment of executive functions, difficulties with spatial cognition, personality change and language deficits. Table 1 summarizes the major contributions to the current knowledge of the cerebellum.