Zebrin Expression in the Cerebellum of Two Crocodilian Species

While in birds and mammals the cerebellum is a highly convoluted structure that consists of numerous transverse lobules, in most amphibians and reptiles it consists of only a single unfolded sheet. Orthogonal to the lobules, the cerebellum is comprised of sagittal zones that are revealed in the pattern of afferent inputs, the projection patterns of Purkinje cells, and Purkinje cell response properties, among other features. The expression of several molecular markers, such as aldolase C, is also parasagittally organized. Aldolase C, also known as zebrin II (ZII), is a glycolytic enzyme expressed in the cerebellar Purkinje cells of the vertebrate cerebellum. In birds, mammals, and some lizards (Ctenophoresspp.), ZII is expressed in a heterogenous fashion of alternating sagittal bands of high (ZII+) and low (ZII–) expression Purkinje cells. In contrast, turtles and snakes express ZII homogenously (ZII+) in their cerebella, but the pattern in crocodilians is unknown. Here, we examined the expression of ZII in two crocodilian species (Crocodylus niloticus and Alligator mississippiensis) to help determine the evolutionary origin of striped ZII expression in vertebrates. We expected crocodilians to express ZII in a striped (ZII+/ZII–) manner because of their close phylogenetic relationship to birds and their larger and more folded cerebellum compared to that of snakes and turtles. Contrary to our prediction, all Purkinje cells in the crocodilian cerebellum had a generally homogenous expression of ZII (ZII+) rather than clear ZII+/– stripes. Our results suggest that either ZII stripes were lost in three groups (snakes, turtles, and crocodilians) or ZII stripes evolved independently three times (lizards, birds, and mammals).

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Zebrin II Is Expressed in Sagittal Stripes in the Cerebellum of Dragon Lizards (Ctenophorus sp.)

Brain Behavior and Evolution ◽

10.1159/000452857 ◽

2016 ◽

Vol 88 (3-4) ◽

pp. 177-186 ◽

Cited By ~ 11

Author(s):

Douglas R. Wylie ◽

Daniel Hoops ◽

Joel W. Aspden ◽

Andrew N. Iwaniuk

Keyword(s):

Purkinje Cells ◽

Posterior Part ◽

Glycolytic Enzyme ◽

Ancestral Condition ◽

Aldolase C ◽

Evolutionary Origins ◽

Zebrin Ii ◽

Heterogeneous Expression ◽

Cerebellar Purkinje Cells

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-). In contrast, in snakes and turtles, ZII is not expressed heterogeneously; rather all Purkinje cells are ZII+. Here, we examined the expression of ZII in the cerebellum of lizards to elucidate the evolutionary origins of ZII stripes in Sauropsida. We focused on the central netted dragon (Ctenophorus nuchalis) but also examined cerebellar ZII expression in 5 other dragon species (Ctenophorus spp.). In contrast to what has been observed in snakes and turtles, we found that in these lizards, ZII is heterogeneously expressed. In the posterior part of the cerebellum, on each side of the midline, there were 3 sagittal stripes consisting of Purkinje cells with high ZII expression (ZII+) alternating with 2 sagittal stripes with weaker ZII expression (ZIIw). More anteriorly, most of the Purkinje cells were ZII+, except laterally, where the Purkinje cells did not express ZII (ZII-). Finally, all Purkinje cells in the auricle (flocculus) were ZII-. Overall, the parasagittal heterogeneous expression of ZII in the cerebellum of lizards is similar to that in mammals and birds, and contrasts with the homogenous ZII+ expression seen in snakes and turtles. We suggest that a sagittal heterogeneous expression of ZII represents the ancestral condition in stem reptiles which was lost in snakes and turtles.

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Zebrin II Expression in the Cerebellum of a Paleognathous Bird, the Chilean Tinamou (Nothoprocta perdicaria)

Brain Behavior and Evolution ◽

10.1159/000380810 ◽

2015 ◽

Vol 85 (2) ◽

pp. 94-106 ◽

Cited By ~ 9

Author(s):

Jeremy R. Corfield ◽

Jeffery Kolominsky ◽

Gonzalo J. Marin ◽

Iulia Craciun ◽

Bridget E. Mulvany-Robbins ◽

...

Keyword(s):

Purkinje Cells ◽

Expression Patterns ◽

Bird Species ◽

Glycolytic Enzyme ◽

Anterior Region ◽

Zebrin Ii ◽

Expression Studies ◽

General Similarity ◽

Cerebellar Purkinje Cells ◽

Nothoprocta Perdicaria

Zebrin II (ZII) is a glycolytic enzyme expressed in cerebellar Purkinje cells. In both mammals and birds, ZII is expressed heterogeneously, such that there are sagittal stripes of Purkinje cells with a high ZII expression (ZII+) alternating with stripes of Purkinje cells with little or no expression (ZII-). To date, ZII expression studies are limited to neognathous birds: pigeons (Columbiformes), chickens (Galliformes), and hummingbirds (Trochilidae). These previous studies divided the avian cerebellum into 5 transverse regions based on the pattern of ZII expression. In the lingular region (lobule I) all Purkinje cells are ZII+. In the anterior region (lobules II-V) there are 4 pairs of ZII+/- stripes. In the central region (lobules VI-VIII) all Purkinje cells are ZII+. In the posterior region (lobules VIII-IX) there are 5-7 pairs of ZII+/- stripes. Finally, in the nodular region (lobule X) all Purkinje cells are ZII+. As the pattern of ZII stripes is quite similar in these disparate species, it appears that it is highly conserved. However, it has yet to be studied in paleognathous birds, which split from the neognaths over 100 million years ago. To better understand the evolution of cerebellar compartmentation in birds, we examined ZII immunoreactivity in a paleognath, the Chilean tinamou (Nothoprocta perdicaria). In the tinamou, Purkinje cells expressed ZII heterogeneously such that there were sagittal ZII+ and ZII- stripes of Purkinje cells, and this pattern of expression was largely similar to that observed in neognathous birds. For example, all Purkinje cells in the lingular (lobule I) and nodular (lobule X) regions were ZII+, and there were 4 pairs of ZII+/- stripes in the anterior region (lobules II-V). In contrast to neognaths, however, ZII was expressed in lobules VI-VII as a series of sagittal stripes in the tinamou. Also unlike in neognaths, stripes were absent in lobule IXab, and all Purkinje cells expressed ZII in the tinamou. The differences in ZII expression between the tinamou and neognaths could reflect behavior, but the general similarity of the expression patterns across all bird species suggests that ZII stripes evolved early in the avian phylogenetic tree.

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The cloning of zebrin II reveals its identity with aldolase C

Development ◽

10.1242/dev.120.8.2081 ◽

1994 ◽

Vol 120 (8) ◽

pp. 2081-2090 ◽

Cited By ~ 2

Author(s):

A.H. Ahn ◽

S. Dziennis ◽

R. Hawkes ◽

K. Herrup

Keyword(s):

Purkinje Cells ◽

Cdna Expression Library ◽

Cdna Clones ◽

Expression Library ◽

Aldolase C ◽

Zebrin Ii ◽

Antibody Staining ◽

Afferent Projections ◽

Biochemical Level ◽

Cerebellar Purkinje Cells

The sagittal organization of the mammalian cerebellum can be observed at the anatomical, physiological and biochemical level. Previous screening of monoclonal antibodies produced in our laboratory has identified two intracellular antigens, zebrin I and II, that occur exclusively in adult cerebellar Purkinje cells. As their name suggests, the zebrin antibody staining of the Purkinje cell population is not uniform. Rather, zebrin-positive Purkinje cells are organized in stripes or bands that run from anterior to posterior across most of the cerebellum; interposed between the zebrin-positive cells are bands of Purkinje cells that are zebrin-negative. Comparison of the position of the antigenic bands with the anatomy of afferent projections suggests that the bands are congruent with the basic developmental and functional ‘compartments’ of the cerebellum. We report the isolation of cDNA clones of the 36 × 10(3) M(r) antigen, zebrin II, by screening of a mouse cerebellum cDNA expression library. Sequence analysis reveals a 98% identity between our clone and the glycolytic isozyme, aldolase C. In order to more rigorously demonstrate the identity of the two proteins, we stained adult cerebellum with an independent monoclonal antibody raised against aldolase C. Anti-aldolase staining occurs in a previously unreported pattern of sagittal bands of Purkinje cells; the pattern is identical to that revealed by the zebrin II monoclonal. Further, in situ hybridization of antisense aldolase C riboprobe shows that the accumulation of zebrin II/aldolase C mRNA corresponds to the pattern of the zebrin antigen in Purkinje cells. Zebrin II/aldolase C gene expression is thus regulated at the level of transcription (or mRNA stability). In light of previous work that has demonstrated the cell-autonomous and developmentally regimented expression of zebrin II, further studies of the regulation of this gene may lead to insights about the determination of cerebellar compartmentation.

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Aldolase C-positive cerebellar Purkinje cells are resistant to delayed death after cerebral trauma and AMPA-mediated excitotoxicity

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2007.05708.x ◽

2007 ◽

Vol 26 (3) ◽

pp. 649-656 ◽

Cited By ~ 16

Author(s):

Jennifer E. Slemmer ◽

Elize D. Haasdijk ◽

Doortje C. Engel ◽

Nikolaus Plesnila ◽

John T. Weber

Keyword(s):

Purkinje Cells ◽

Aldolase C ◽

Cerebral Trauma ◽

Delayed Death ◽

Cerebellar Purkinje Cells

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Modulation of complex spike activity differs between zebrin-positive and -negative Purkinje cells in the pigeon cerebellum

Journal of Neurophysiology ◽

10.1152/jn.00797.2017 ◽

2018 ◽

Vol 120 (1) ◽

pp. 250-262 ◽

Cited By ~ 4

Author(s):

Rebecca M. Long ◽

Janelle M. P. Pakan ◽

David J. Graham ◽

Peter L. Hurd ◽

Cristian Gutierrez-Ibañez ◽

...

Keyword(s):

Molecular Markers ◽

Purkinje Cells ◽

Optic Flow ◽

Spike Activity ◽

Functional Unit ◽

Mossy Fiber ◽

Vestibular Nuclei ◽

Uniform Structure ◽

Complex Spike ◽

Zebrin Ii

The cerebellum is organized into parasagittal zones defined by its climbing and mossy fiber inputs, efferent projections, and Purkinje cell (PC) response properties. Additionally, parasagittal stripes can be visualized with molecular markers, such as heterogeneous expression of the isoenzyme zebrin II (ZII), where sagittal stripes of high ZII expression (ZII+) are interdigitated with stripes of low ZII expression (ZII−). In the pigeon vestibulocerebellum, a ZII+/− stripe pair represents a functional unit, insofar as both ZII+ and ZII− PCs within a stripe pair respond best to the same pattern of optic flow. In the present study, we attempted to determine whether there were any differences in the responses between ZII+ and ZII− PCs within a functional unit in response to optic flow stimuli. In pigeons of either sex, we recorded complex spike activity (CSA) from PCs in response to optic flow, marked recording sites with a fluorescent tracer, and determined the ZII identity of recorded PCs by immunohistochemistry. We found that CSA of ZII+ PCs showed a greater depth of modulation in response to the preferred optic flow pattern compared with ZII− PCs. We suggest that these differences in the depth of modulation to optic flow stimuli are due to differences in the connectivity of ZII+ and ZII− PCs within a functional unit. Specifically, ZII+ PCs project to areas of the vestibular nuclei that provide inhibitory feedback to the inferior olive, whereas ZII− PCs do not. NEW & NOTEWORTHY Although the cerebellum appears to be a uniform structure, Purkinje cells (PCs) are heterogeneous and can be categorized on the basis of the expression of molecular markers. These phenotypes are conserved across species, but the significance is undetermined. PCs in the vestibulocerebellum encode optic flow resulting from self-motion, and those that express the molecular marker zebrin II (ZII+) exhibit more sensitivity to optic flow than those that do not express zebrin II (ZII−).

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Cerebellar modules operate at different frequencies

eLife ◽

10.7554/elife.02536 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 147

Author(s):

Haibo Zhou ◽

Zhanmin Lin ◽

Kai Voges ◽

Chiheng Ju ◽

Zhenyu Gao ◽

...

Keyword(s):

Purkinje Cells ◽

Cerebellar Cortex ◽

Distribution Patterns ◽

Glycolytic Enzyme ◽

Spike Frequency ◽

Intrinsic Activity ◽

Aldolase C ◽

Simple Spike ◽

The Difference ◽

Cerebellar Modules

Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. In this study, we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with their expression of the glycolytic enzyme aldolase C or zebrin. Simple spike and complex spike frequencies were significantly higher in Purkinje cells located in zebrin-negative than zebrin-positive modules. The difference in simple spike frequency persisted when the synaptic input to, but not intrinsic activity of, Purkinje cells was manipulated. Blocking TRPC3, the effector channel of a cascade of proteins that have zebrin-like distribution patterns, attenuated the simple spike frequency difference. Our results indicate that zebrin-discriminated cerebellar modules operate at different frequencies, which depend on activation of TRPC3, and that this property is relevant for all cerebellar functions.

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Patterned expression of Pannexin 1 channels in the adult cerebellar Purkinje cells

10.1101/453738 ◽

2018 ◽

Author(s):

Visou Ady ◽

David Dubayle ◽

Pascale Le Blanc ◽

Valery Shestopalov ◽

Claude Meunier ◽

...

Keyword(s):

Cell Death ◽

Purkinje Cells ◽

Cell Communication ◽

Cerebellar Nuclei ◽

Modular Architecture ◽

Pannexin 1 ◽

Zebrin Ii ◽

Dependent Cell ◽

Cerebellar Purkinje Cells ◽

Ensemble Activity

AbstractPannexin1 (PanX1) are recently discovered proteins that can form large pore channels at the cell surface. They have been implicated in ATP-dependent cell-to-cell communication and in several pathophysiological processes such as inflammation, cell death and epilepsy. Using immunohistochemistry in the adult mouse, we describe the presence of PanX1 in the deep cerebellar nuclei, in large cells of the granular layer, presumably Golgi interneurones, in some Bergmann glia radial processes as well as in the soma and dendrites of Purkinje cells. In the latter, PanX1, like many other proteins, distribute heterogeneously. Only Zebrin II-positive Purkinje cells express PanX1, in accordance with the so-called “zebra-striped” modular architecture of the cerebellum. This distribution in zebra-stripes suggest that PanX1 may contribute to the control of ensemble activity within cerebellar microdomains or to the response of Purkinje cell to excitotoxicity and cell-death messages.

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Ultrastorcture of Cerebellar Purkinje Cells in Rats Subjected To Partial Global Cerebral Ischemia

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120060 ◽

1985 ◽

Vol 43 ◽

pp. 674-675

Author(s):

R.V.W. Dimlich ◽

M.H. Biros

Keyword(s):

Cerebral Ischemia ◽

Purkinje Cells ◽

Cell Types ◽

Microscopic Level ◽

Global Cerebral Ischemia ◽

Light Microscopic Level ◽

Cerebellar Damage ◽

Cerebellar Injury ◽

Cerebellar Purkinje Cells ◽

Cell Changes

In severe cerebral ischemia, Purkinje cells of the cerebellum are one of the cell types most vulnerable to anoxic damage. In the partial (forebrain) global ischemic (PGI) model of the rat, Paljärvi noted at the light microscopic level that cerebellar damage is inconsistant and when present, milder than in the telencephalon, diencephalon and rostral brain stem. Cerebellar injury was observed in 3 of 4 PGI rats following 5 minutes of reperfusion but in none of the rats after 90 min of reperfusion. To evaluate a time between these two extremes (5 and 90 min), the present investigation used the PGI model to study the effects of ischemia on the ultrastructure of cerebellar Purkinje cells in rats that were sacrificed after 30 min of reperfusion. This time also was chosen because lactic acid that is thought to contribute to ischemic cell changes in PGI is at a maximum after 30 min of reperfusion.

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