Cerebellum Lecture: the Cerebellar Nuclei-Core of the Cerebellum.

The cerebellum is a key player in many brain functions and a major topic of neuroscience research. However, the cerebellar nuclei (CN), the main output structures of the cerebellum, are often overlooked. This neglect is because research on the cerebellum typically focuses on the cortex and tends to treat the CN as relatively simple output nuclei conveying an inverted signal from the cerebellar cortex to the rest of the brain.

Early Cerebellar Development in Relation to the Trigeminal System.

Despite the wealth of knowledge of adult cerebellar connectivity, little is known about the developmental mechanisms that underpin its development. Early connectivity is important because it is the foundation of the neural networks crucial for neuronal function and serves as a scaffold on which later tracts form. Conventionally, it is believed that afferents from the vestibular system are the first to invade the cerebellum, at embryonic days (E) 11-E12/13 in mice, where they target the new born Purkinje cells.

Cerebellar Patterning Defects in Mutant Mice.

The cerebellar cortex is highly compartmentalized and serves as a remarkable model for pattern formation throughout the brain. In brief, the adult cerebellar cortex is subdivided into five anteroposterior units-transverse zones-and subsequently, each zone is divided into ∼20 parasagittal stripes. Zone-and-stripe pattern formation involves the interplay of two parallel developmental pathways-one for inhibitory neurons, the second for excitatory.

Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum.

Granule cells (GCs) are the most numerous cell type in the cerebellum and indeed, in the brain: at least 99% of all cerebellar neurons are granule cells. In this review article, we first consider the formation of the upper rhombic lip, from which all granule cell precursors arise, and the way by which the upper rhombic lip generates the external granular layer, a secondary germinal epithelium that serves to amplify the upper rhombic lip precursors. Next, we review the mechanisms by which postmitotic granule cells are generated in the external granular layer and migrate radially to settle in the granular layer.

Dynamic Expression and New Functions of Early B Cell Factor 2 in Cerebellar Development.

The collier/Olf1/EBF family genes encode helix-loop-helix transcription factors (TFs) highly conserved in evolution, initially characterized for their roles in the immune system and in various aspects of neural development. The Early B cell Factor 2 (Ebf2) gene plays an important role in the establishment of cerebellar cortical topography and in Purkinje cell (PC) subtype specification. In the adult cerebellum, Ebf2 is expressed in zebrin II (ZII)-negative PCs, where it suppresses the ZII+ molecular phenotype.

Early trigeminal ganglion afferents enter the cerebellum before the Purkinje cells are born and target the nuclear transitory zone.

In the standard model for the development of climbing and mossy fiber afferent pathways to the cerebellum, the ingrowing axons target the embryonic Purkinje cell somata (around embryonic ages (E13-E16 in mice). In this report, we describe a novel earlier stage in afferent development. Immunostaining for a neurofilament-associated antigen (NAA) reveals the early axon distributions with remarkable clarity.

Correction to: Cerebellar Modules and Their Role as Operational Cerebellar Processing Units: A Consensus paper.

In the original version of this paper, the Title should have been written with "A Consensus paper" to read "Cerebellar Modules and Their Role as Operational Cerebellar Processing Units: A Consensus paper".

Cerebellar Modules and Their Role as Operational Cerebellar Processing Units: A Consensus paper [corrected].

The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give their insights on the structure and function of cerebellar modules, with the aim of providing an up-to-date review of the extensive literature on this subject.

The Ferdinando Rossi Memorial Lecture: Zones and Stripes-Pattern Formation in the Cerebellum.

The cerebellum has a complex architecture-highly reproducible and conserved through evolution. Cerebellar architecture is organized around the Purkinje cell. Purkinje cells in the mouse cerebellum come in many different subtypes, identifiable by expression markers, sensitivity to mutation, etc.

regulates cell cycle progression, the mode of cell division and the DNA-damage response in Purkinje neuron progenitors.

The gene encodes a 30-zinc-finger transcription factor involved in key developmental pathways. Although null mutants develop cerebellar malformations, the underlying mechanism remains unknown. mutations are associated with Joubert Syndrome, a ciliopathy causing cerebellar vermis hypoplasia and ataxia.

Maternal immune activation produces cerebellar hyperplasia and alterations in motor and social behaviors in male and female mice.

There have been suggestions that maternal immune activation is associated with alterations in motor behavior in offspring. To explore this further, we treated pregnant mice with polyinosinic:polycytidylic acid (poly(I:C)), a viral mimetic that activates the innate immune system, or saline on embryonic days 13-15. At postnatal day (P) 18, offspring cerebella were collected from perfused brains and immunostained as whole-mounts for zebrin II.

Zebrin II / aldolase C expression in the cerebellum of the western diamondback rattlesnake (Crotalus atrox).

Aldolase C, also known as Zebrin II (ZII), is a glycolytic enzyme that is expressed in cerebellar Purkinje cells of the vertebrate cerebellum. In both mammals and birds, ZII is expressed heterogeneously, such that there are sagittal stripes of Purkinje cells with high ZII expression (ZII+), alternating with stripes of Purkinje cells with little or no expression (ZII-). The patterns of ZII+ and ZII- stripes in the cerebellum of birds and mammals are strikingly similar, suggesting that it may have first evolved in the stem reptiles.

Compartmentation of the cerebellar cortex: adaptation to lifestyle in the star-nosed mole Condylura cristata.

The adult mammalian cerebellum is histologically uniform. However, concealed beneath the simple laminar architecture, it is organized rostrocaudally and mediolaterally into complex arrays of transverse zones and parasagittal stripes that is both highly reproducible between individuals and generally conserved across mammals and birds. Beyond this conservation, the general architecture appears to be adapted to the animal's way of life.

Purkinje cell stripes and long-term depression at the parallel fiber-Purkinje cell synapse.

The cerebellar cortex comprises a stereotyped array of transverse zones and parasagittal stripes, built around multiple Purkinje cell subtypes, which is highly conserved across birds and mammals. This architecture is revealed in the restricted expression patterns of numerous molecules, in the terminal fields of the afferent projections, in the distribution of interneurons, and in the functional organization. This review provides an overview of cerebellar architecture with an emphasis on attempts to relate molecular architecture to the expression of long-term depression (LTD) at the parallel fiber-Purkinje cell (pf-PC) synapse.

The neuroplastin adhesion molecules are accessory proteins that chaperone the monocarboxylate transporter MCT2 to the neuronal cell surface.

Background: The neuroplastins np65 and np55 are two synapse-enriched immunoglobulin (Ig) superfamily adhesion molecules that contain 3 and 2 Ig domains respectively. Np65 is implicated in long term, activity dependent synaptic plasticity, including LTP. Np65 regulates the surface expression of GluR1 receptor subunits and the localisation of GABA(A) receptor subtypes in hippocampal neurones.

The compartmental restriction of cerebellar interneurons.

The Purkinje cells (PC's) of the cerebellar cortex are subdivided into multiple different molecular phenotypes that form an elaborate array of parasagittal stripes. This array serves as a scaffold around which afferent topography is organized. The ways in which cerebellar interneurons may be restricted by this scaffolding are less well-understood.

Purkinje cell compartmentalization in the cerebellum of the spontaneous mutant mouse dreher.

The cerebellar morphological phenotype of the spontaneous neurological mutant mouse dreher (Lmx1a(dr-J)) results from cell fate changes in dorsal midline patterning involving the roof plate and rhombic lip. Positional cloning revealed that the gene Lmx1a, which encodes a LIM homeodomain protein, is mutated in dreher, and is expressed in the developing roof plate and rhombic lip. Loss of Lmx1a causes reduction of the roof plate, an important embryonic signaling center, and abnormal cell fate specification within the embryonic cerebellar rhombic lip.

Antigenic compartmentation of the cerebellar cortex in an Australian marsupial, the tammar wallaby Macropus eugenii.

The mammalian cerebellar cortex is apparently uniform in composition, but a complex heterogeneous pattern can be revealed by using biochemical markers such as zebrin II/aldolase C, which is expressed by a subset of Purkinje cells that form a highly reproducible array of transverse zones and parasagittal stripes. The architecture revealed by zebrin II expression is conserved among many taxa of birds and mammals. In this report zebrin II immunohistochemistry has been used in both section and whole-mount preparations to analyze the cerebellar architecture of the Australian tammar wallaby (Macropus eugenii).

Wholemount immunohistochemistry for revealing complex brain topography.

The repeated and well-understood cellular architecture of the cerebellum make it an ideal model system for exploring brain topography. Underlying its relatively uniform cytoarchitecture is a complex array of parasagittal domains of gene and protein expression. The molecular compartmentalization of the cerebellum is mirrored by the anatomical and functional organization of afferent fibers.

Patterned Purkinje cell loss in the ataxic sticky mouse.

The ataxic sticky (sti/sti) mouse is a spontaneous autosomal recessive mutant resulting from a disruption in the editing domain of the alanyl-tRNA synthetase (Aars) gene. The sticky phenotype is characterized by a small body size, a characteristic unkempt coat and neurological manifestations including marked tremor and ataxia starting at 6 weeks of age. The present study was undertaken to examine the spatiotemporal features of Purkinje cell degeneration in the sticky mouse.

Zac1 plays a key role in the development of specific neuronal subsets in the mouse cerebellum.

Background: The cerebellum is composed of a diverse array of neuronal subtypes. Here we have used a candidate approach to identify Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, as a new player in the transcriptional network required for the development of a specific subset of cerebellar nuclei and a population of Golgi cells in the cerebellar cortex.

Results: We found that Zac1 has a complex expression profile in the developing cerebellum, including in two proliferating progenitor populations; the cerebellar ventricular zone and the external granular layer overlying posterior cerebellar lobules IX and X.

On the architecture of the posterior zone of the cerebellum.

The mammalian cerebellum is histologically uniform. However, underlying the simple laminar architecture is a complex arrangement of parasagittal stripes and transverse zones that can be revealed by the expression of many molecules, in particular, zebrin II/aldolase C. By using a combination of Purkinje cell antigenic markers and afferent tracing, four transverse zones have been identified: in mouse, these are the anterior zone (∼lobules I-V), the central zone (∼lobules VI-VII), the posterior zone (PZ: ∼lobules VIII-dorsal IX), and the nodular zone (∼ventral lobule IX + lobule X).

Expression of the IP3R1 promoter-driven nls-lacZ transgene in Purkinje cell parasagittal arrays of developing mouse cerebellum.

The cerebellar Purkinje cell monolayer is organized into heterogeneous Purkinje cell compartments that have different molecular compositions. Here we describe a transgenic mouse line, 1NM13, that shows heterogeneous transgene expression in parasagittal Purkinje cell arrays. The transgene consists of a nuclear localization signal (nls) fused to the beta-galactosidase (lacZ) composite gene driven by the type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1) gene promoter.