Detailed Expression Pattern of Aldolase C (Aldoc) in the Cerebellum, Retina and Other Areas of the CNS Studied in Aldoc-Venus Knock-In Mice

Abstract

Aldolase C (Aldoc, also known as “zebrin II”), a brain type isozyme of a glycolysis enzyme, is expressed heterogeneously in subpopulations of cerebellar Purkinje cells (PCs) that are arranged longitudinally in a complex striped pattern in the cerebellar cortex, a pattern which is closely related to the topography of input and output axonal projections. Here, we generated knock-in Aldoc-Venus mice in which Aldoc expression is visualized by expression of a fluorescent protein, Venus. Since there was no obvious phenotypes in general brain morphology and in the striped pattern of the cerebellum in mutants, we made detailed observation of Aldoc expression pattern in the nervous system by using Venus expression in Aldoc-Venus heterozygotes. High levels of Venus expression were observed in cerebellar PCs, cartwheel cells in the dorsal cochlear nucleus, sensory epithelium of the inner ear and in all major types of retinal cells, while moderate levels of Venus expression were observed in astrocytes and satellite cells in the dorsal root ganglion. The striped arrangement of PCs that express Venus to different degrees was carefully traced with serial section alignment analysis and mapped on the unfolded scheme of the entire cerebellar cortex to re-identify all individual Aldoc stripes. A longitudinally striped boundary of Aldoc expression was first identified in the mouse flocculus, and was correlated with the climbing fiber projection pattern and expression of another compartmental marker molecule, heat shock protein 25 (HSP25). As in the rat, the cerebellar nuclei were divided into the rostrodorsal negative and the caudoventral positive portions by distinct projections of Aldoc-positive and negative PC axons in the mouse. Identification of the cerebellar Aldoc stripes in this study, as indicated in sample coronal and horizontal sections as well as in sample surface photos of whole-mount preparations, can be referred to in future experiments.

Redefining the cerebellar cortex as an assembly of non-uniform Purkinje cell microcircuits

“…3). Recent data from a knock-in mouse model suggests that the levels of zebrin II gene expression may vary across the bands in which it is expressed 63 . However, the general banding pattern is highly consistent and conserved across mammals and birds 10, 64 .…”

Depressed by Learning—Heterogeneity of the Plasticity Rules at Parallel Fiber Synapses onto Purkinje Cells

“…The discovery of the tuning of LTD for different parallel fiber-Climbing fiber intervals illustrates how existing knowledge of the broader circuits supporting simple cerebellum-dependent forms of learning can be leveraged to inform experimental manipulations in vitro that can uncover new features of synaptic learning rules. Moreover, we can draw on a vast literature on the molecular mechanisms that support parallel fiber-to-Purkinje cell LTD [10,11,38,39,44,106,122,18,31–37], and on the heterogeneity of Purkinje cells [123,124,133–137,125–132]. Thus, studies of plasticity at the cerebellar Purkinje cells’ synapses offers unique insights and opportunities to move beyond broad concepts of Hebbian and anti-Hebbian plasticity to a more sophisticated understanding of the complex rules governing plasticity at synapses in a behaving animal undergoing learning.…”

Early development of the nervous system of the eutherian <i>Tupaia belangeri</i>

“…Other groups have subsequently studied zebrin-IIimmunoreactive cerebellar compartments in order to carry out the following investigations: (1) interspecific comparison with the tammar wallaby (Macropus eugenii) (Marzban et al 2012), microchiropteran bats (Kim et al, 2009), hummingbirds (Aves: Trochilidae) (Iwaniuk et al, 2009), chicks (Gallus domesticus) (Marzban et al, 2010), pigeons (Columba livia) (Pakan et al, 2007; for an overview, see Marzban and Hawkes, 2011); (2) visualization of aldolase C with fluorescence through gene manipulation with the help of aldolase CVenus knock-in mice to facilitate studies on cerebellar compartmentalization (Fujita et al, 2014); (3) presentation of parasagittal stripes in the vermis which, complementary to zebrin II, are immunoreactive for neurofilament H (Demilly et al, 2011); (4) identification of links between the olivocerebellar projection and zebrin-immunoreactive compartments in the laboratory mouse (Sugihara and Quy, 2007) and in marmoset (Callithrix jacchus) (Fujita et al, 2010); (5) clarification of the role played by the helix-loop-helix (HLH) transcription factor early B-cell factor 2 (EBF2) (Croci et al, 2006); and (6) evaluation of the cerebellar connectivity in spinocerebellar ataxia type 1 (Solodkin et al, 2011). The second main research area of Wolfgang Knabe and colleagues, whose roots date back to the former anatomical department of Hans-Jürg Kuhn, continued previous projects on the retina, then served as a bridge between the retina and the forebrain, and, thereafter, was successively expanded to include the entire brain, spinal cord, neural crest, and the placodes.…”