Introduction

“No matter how advanced the techniques developed to study the cerebellum, they will succeed in painting the true picture of cerebellar function only if they are based on the facts of cerebellar anatomy.” Robert S. Dow, MD, PhD, 1972 [1]

A poster presented at the annual meeting of the Society for Neuroscience in 1983 (later publishing in JCN) detailed the arrangement of direct projections from the hypothalamus to the cerebellar cortex and from the cerebellar nuclei to the hypothalamus. A number of colleagues queried the authors “If these connections have always been there, why have others not seen them?” The authors responded that the cerebellum people discard the hypothalamus, and the hypothalamus people discard the cerebellum; they do not look for the unexpected. Such is the case for the unipolar brush cell, a neglected and unexpected neuron in the cerebellar cortex.

Many highly regarded scientists have examined the structure of the cerebellar cortex using a wide range of methods and techniques for many years and have made numerous important observations. What Mugnaini and Floris named the unipolar brush cell, existed in these early studies. However, it remained for their critical analysis, dogged scientific pursuit, and insight to recognize this cell as a unique structural and functional entity; they looked for, and they anticipated, the unexpected. This initial report and those that followed from Mugnaini’s laboratory, has resulted in the unipolar brush cell being well recognized in the scientific literature and appearing in neuroscience textbooks. Most importantly, this term has been accepted by the International Federation of Associations of Anatomists (IFAA) and appears in Terminologia Histologica as an officially recognized histologic cell type ([2], p. 96). A further validation of the widespread acceptance of the unipolar brush cell is seen by its inclusion in a number of chapters of the Handbook of the Cerebellum and Cerebellar Disorders [3].

In this early paper, Mugnaini and Floris used mice, rats, cats, and rhesus monkeys. This approach nullified a potential criticism of novel discoveries in the modern era, this being that new observations may have eluded detection because they are species specific. The unipolar brush cell (UBC) is common to all vertebrates examined to date including human.

Mugnaini and Floris [4] described the general characteristics of the UBC in this report. First, the UBC at 9–12 μm is slightly larger than granule cells, has short distinctive dendritic appendages, and an axon that may arise from the cell body, dendritic trunk, or distal dendrites. Second, UBEs are most commonly found in the flocculonodular lobe, ventral uvula, ventral paraflocculus, lingual, and less so in portions of the vermis; these cerebellar cortical regions are generally considered to be largely co-extensive with the vestibulocerebellum as they receive afferents from and send efferents to the vestibular nuclei. Third, UBCs have synaptic relations with each other and with granule cells, Golgi cells, and mossy fiber rosettes. Fourth, based on their distribution and synaptic interactions, Mugnaini and Floris [4] suggested that the UBCs were intimately involved in pathways and loops that modulate/control various aspects of eye movement.

A number of earlier studies, using several methods, had reported data suggestive of a cerebellar cell type that was not strictly consistent with the features of granule, Golgi, and Purkinje cells ([5–8]; and others). Altman and Bayer [5] called the presumptive UBC a “pale cell”. Mugnaini and his colleagues confirmed these fragmented early reports and conducted a large series of studies to characterize the UBC morphologically and functionally. They described the UBCs synaptic relationships, locations within the lobules and folia of the cerebellum, immunocytochemistry, important electron microscopic features, and neurotransmitters. These studies have been corroborated by subsequent investigators and have opened up opportunities for future studies that may focus on the function of UBCs, particularly in the arena of disorders of eye movement. Most of this extensive research effort to elucidate the UBC is summarized by Diño et al. [9] and Mugnani et al. [10].

The original paper of Mugnaini and Floris is reprinted here for the enjoyment of the readership of The Cerebellum as part of this Special Issue honoring the scientific accomplishments and contributions of Professor Enrico Mugnaini. It is anticipated that our readers will enjoy reacquainting themselves with this important paper and reading the Commentary that follows, see [11].