Commentary on "E. Mugnaini and A. Floris, the unipolar brush cell: a neglected neuron of the mammalian cerebellar cortex. J Comp Neurol, 339:174-180, 1994".

Abstract

One of the accomplishments of Enrico’s laboratory in the late 1980s—then at the University of Connecticut in Storrs—was demonstrating that cerebellar-like neuronal microcircuits exist in the acoustic brainstem [1]. This was done by coupling classic neuroanatomical methods (such as electron microscopy and tract tracing) to what were then two novel techniques: immunocytochemical cell-specific neuronal labeling and the use of transgenicmice. Thus, in the early 1990s, the laboratory focused on clarifying the precise organization, input and output, and evolutionary significance of the recently identified cerebellar-like microcircuit in the mammalian dorsal cochlear nuclear complex (DCN). At the same time, Enrico’s laboratory continued its long-standing interest in cerebellar organization and development (Enrico’s cerebellar grant was continuously funded for what might be a record-setting 38 years [2]). Like most serendipitous scientific discoveries, the unipolar brush cell’s (UBC’s) identification was both unforeseen and unplanned, but nevertheless the by-product of a sagacious and prepared mind. Because the Purkinje cell markers used in the DCN studies were mostly calcium-binding proteins (calbindin, PEP-19, and parvalbumin), Enrico constantly reached out to potential collaborators who worked with this family of proteins. Among them was David Jacobowitz from the NIH, who sent us antibodies to the calcium-binding protein calretinin, which turned out to be a cell-marker for what we now know as one of the UBC subtypes [3]. As a beginning graduate student, I had no notion of what we had found. But Enrico immediately put it into context, recalling studies describing novel cerebellar neurons primarily localized to the vestibulocerebellum: Altman and Bayer’s pale cells [4], Susan Hockfield’s Rat-302 cells [5], Munoz’monodendritic neurons [6], and the secretogranin-positive cells described by Cozzi et al. [7]. Bringing to bear his expertise and encyclopedic knowledge of classic neuroanatomy and electron microscopy, Enrico turned his attention to the UBC’s ultrastructure and synaptology [8] and quickly realized that previous studies (including his own) had already described UBC features but mistakenly attributed them to other cerebellar cell types. For example, the Bhairy dendrites^ and ringlet subunits that he had previously described for Golgi cells of the cat cerebellum [9], and the giant mossy fiber Ben marron^ synapse previously described on the postsynaptic Golgi II neuron by ChanPalay and Palay [10]: all of these turned out to be UBC hallmarks. Other telltale features of the UBC revealed by a combination of preand post-embedding immunoelectron microscopy included a high density of large dense-cored vesicles; an abundance of high molecular weight neurofilament protein, whose dephosphorylated variant was later identified as the Rat-302 protein [11]; a postsynaptic microfilamentous actin web under the giant mossy fiber-UBC synapse [12]; and the The Introduction article of Cerebellar Classic XI is available at http:// dx.doi.org/10.1007/s12311-015-0661-0