Stacey L Reeber

Baylor College of Medicine, Houston, Texas, United States

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Publications (14)46.86 Total impact

  • Stacey L Reeber · Marife Arancillo · Roy V Sillitoe
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    ABSTRACT: Cerebellar circuits are patterned into an array of topographic parasagittal domains called zones. Zones are best revealed by gene expression, circuit anatomy, and cellular degeneration patterns. Thus far, the study of zones has been focused heavily on how neurons are organized. Because of this, detailed neuronal patterning maps have been established for Purkinje cells, granule cells, Golgi cells, unipolar brush cells, and also for the terminal field organization of climbing fiber and mossy fiber afferents. In comparison, however, it remains poorly understood if glial cells are also organized into zones. We have identified an Npy-Gfp BAC transgenic mouse line (Tau-Sapphire Green fluorescent protein (Gfp) is under the control of the neuropeptide Y (Npy) gene regulatory elements) that can be used to label Bergmann glial cells with Golgi-like resolution. In these adult transgenic mice, we found that Npy-Gfp expression was localized to Bergmann glia mainly in lobules VI/VII and IX/X. Using double immunofluorescence, we show that in these lobules, Npy-Gfp expression in the Bergmann glia overlaps with the pattern of the small heat shock protein HSP25, a Purkinje cell marker for zones located in lobules VI/VII and IX/X. Developmental analysis starting from the day of birth showed that HSP25 and Npy-Gfp expression follow a similar program of spatial and temporal patterning. However, loss of Npy signaling did not alter the patterning of Purkinje cell zones. We conclude that Bergmann glial cells are zonally organized and their patterns are restricted by boundaries that also confine cerebellar neurons into a topographic circuit map.
    No preview · Article · Jun 2014 · The Cerebellum
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    Stacey L Reeber · Tom S Otis · Roy V Sillitoe
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    ABSTRACT: The cerebellum has a well-established role in maintaining motor coordination and studies of cerebellar learning suggest that it does this by recognizing neural patterns, which it uses to predict optimal movements. Serious damage to the cerebellum impairs this learning and results in a set of motor disturbances called ataxia. However, recent work implicates the cerebellum in cognition and emotion, and it has been argued that cerebellar dysfunction contributes to non-motor conditions such as autism spectrum disorders (ASD). Based on human and animal model studies, two major questions arise. Does the cerebellum contribute to non-motor as well as motor diseases, and if so, how does altering its function contribute to such diverse symptoms? The architecture and connectivity of cerebellar circuits may hold the answers to these questions. An emerging view is that cerebellar defects can trigger motor and non-motor neurological conditions by globally influencing brain function. Furthermore, during development cerebellar circuits may play a role in wiring events necessary for higher cognitive functions such as social behavior and language. We discuss genetic, electrophysiological, and behavioral evidence that implicates Purkinje cell dysfunction as a major culprit in several diseases and offer a hypothesis as to how canonical cerebellar functions might be at fault in non-motor as well as motor diseases.
    Full-text · Article · Nov 2013 · Frontiers in Systems Neuroscience
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    ABSTRACT: The cerebellum is organized into zonal circuits that are thought to regulate ongoing motor behavior. Recent studies suggest that neuronal birthdates, gene expression patterning, and apoptosis control zone formation. Importantly, developing Purkinje cell zones are thought to provide the framework upon which afferent circuitry is organized. Yet, it is not clear whether altering the final placement of Purkinje cells affects the assembly of circuits into topographic zones. To gain insight into this problem, we examined zonal connectivity in scrambler mice; spontaneous mutants that have severe Purkinje cell ectopia due to the loss of reelin-disabled1 signaling. We used immunohistochemistry and neural tracing to determine whether displacement of Purkinje cell zones into ectopic positions triggers defects in zonal connectivity within sensory-motor circuits. Despite the abnormal placement of more than 95% of Purkinje cells in scrambler mice, the complementary relationship between molecularly distinct Purkinje cell zones is maintained, and consequently, afferents are targeted into topographic circuits. These data suggest that although loss of disabled1 distorts the Purkinje cell map, its absence does not obstruct the formation of zonal circuits. These findings support the hypothesis that Purkinje cell zones play an essential role in establishing afferent topography.
    Preview · Article · Jul 2013 · Frontiers in Neural Circuits
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    ABSTRACT: The cerebellum has a simple tri-laminar structure that is comprised of relatively few cell types. Yet, its internal micro-circuitry is anatomically, biochemically, and functionally complex. The most striking feature of cerebellar circuit complexity is its compartmentalized topography. Each cell type within the cerebellar cortex is organized into an exquisite map; molecular expression patterns, dendrite projections, and axon terminal fields divide the medial-lateral axis of the cerebellum into topographic sagittal zones. Here, we discuss the mechanisms that establish zones and highlight how gene expression and neural activity contribute to cerebellar pattern formation. We focus on the olivocerebellar system because its developmental mechanisms are becoming clear, its topographic termination patterns are very precise, and its contribution to zonal function is debated. This review deconstructs the architecture and development of the olivocerebellar pathway to provide an update on how brain circuit maps form and function.
    Full-text · Article · Dec 2012 · Frontiers in Neural Circuits
  • Stacey L Reeber · Kevin J O'Donovan
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    ABSTRACT: Understanding how cells from different neuronal and glial lineages contribute to functional circuits has been complicated by the difficulty in tracking cells as they integrate into brain circuits. Sudarov et al. (J Neurosci 31(30):11055-11069, 2011) used a powerful genetics-based lineage marking approach to birth date ventricular zone-derived cells in the mouse cerebellum. The authors use their novel tools to elucidate the spatial and temporal dynamics of how distinct ventricular zone lineages are generated and assemble into the cerebellar microcircuitry. In this journal club, we discuss and evaluate the author's major findings.
    No preview · Article · Aug 2012 · The Cerebellum
  • Joshua J White · Stacey L Reeber · Richard Hawkes · Roy V Sillitoe
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    ABSTRACT: 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. To fully appreciate the complexity of cerebellar organization we previously refined a wholemount staining approach for high throughput analysis of patterning defects in the mouse cerebellum. This protocol describes in detail the reagents, tools, and practical steps that are useful to successfully reveal protein expression patterns in the adult mouse cerebellum by using wholemount immunostaining. The steps highlighted here demonstrate the utility of this method using the expression of zebrinII/aldolaseC as an example of how the fine topography of the brain can be revealed in its native three-dimensional conformation. Also described are adaptations to the protocol that allow for the visualization of protein expression in afferent projections and large cerebella for comparative studies of molecular topography. To illustrate these applications, data from afferent staining of the rat cerebellum are included.
    No preview · Article · Apr 2012 · Journal of Visualized Experiments
  • Stacey L Reeber · Samrawit A Gebre · Nika Filatova · Roy V Sillitoe
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    ABSTRACT: Neural circuits are organized into functional topographic maps. In order to visualize complex circuit architecture we developed an approach to reliably label the global patterning of multiple topographic projections. The cerebellum is an ideal model to study the orderly arrangement of neural circuits. For example, the compartmental organization of spinocerebellar mossy fibers has proven to be an indispensable system for studying mossy fiber patterning. We recently showed that wheat germ agglutinin (WGA) conjugated to Alexa 555 and 488 can be used for tracing spinocerebellar mossy fiber projections in developing and adult mice (Reeber et al. 2011). We found three major properties that make the WGA-Alexa tracers desirable tools for labeling neural projections. First, Alexa fluorophores are intense and their brightness allows for wholemount imaging directly after tracing. Second, WGA-Alexa tracers label the entire trajectory of developing and adult neural projections. Third, WGA-Alexa tracers are rapidly transported in both retrograde and anterograde directions. Here, we describe in detail how to prepare the tracers and other required tools, how to perform the surgery for spinocerebellar tracing and how best to image traced projections in three dimensions. In summary, we provide a step-by-step tracing protocol that will be useful for deciphering the organization and connectivity of functional maps not only in the cerebellum but also in the cortex, brainstem, and spinal cord.
    No preview · Article · Nov 2011 · Journal of Visualized Experiments
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    ABSTRACT: Despite the general uniformity in cellular composition of the adult cerebellum (Cb), the expression of proteins such as ZebrinII/AldolaseC and the small heat shock protein HSP25 reveal striking patterns of parasagittal Purkinje cell (PC) stripes. Based on differences in the stripe configuration within subsets of lobules, the Cb can be further divided into four anterior-posterior transverse zones: anterior zone (AZ) = lobules I-V, central zone (CZ) = lobules VI-VII, posterior zone (PZ) = lobules VIII and anterior IX, and the nodular zone (NZ) = lobules posterior IX-X. Here we used whole-mount and tissue section immunohistochemistry to show that neurofilament heavy chain (NFH) expression alone divides all lobules of the mouse Cb into a complex series of parasagittal stripes of PCs. We revealed that the striped pattern of NFH in the vermis of the AZ and PZ was complementary to ZebrinII and phospholipase C ß3 (PLCß3), and corresponded to phospholipase C ß4 (PLCß4). In the CZ and NZ the stripe pattern of NFH was complementary to HSP25 and corresponded to PLCß3. The boundaries of the NFH stripes were not always sharply delineated. Instead, a gradual decrease in NFH expression was observed toward the edges of particular stripes, resulting in domains comprised of overlapping expression patterns. Furthermore, the terminal field distributions of mossy and climbing fibers had a complex but consistent topographical alignment with NFH stripes. In summary, NFH expression reveals an exquisite level of Cb stripe complexity that respects the transverse zone divisions and delineates an intricately patterned target field for Cb afferents.
    No preview · Article · Sep 2011 · The Cerebellum
  • Samrawit A Gebre · Stacey L Reeber · Roy V Sillitoe
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    ABSTRACT: The cerebellum receives sensory signals from spinocerebellar (lower limbs) and dorsal column nuclei (upper limbs) mossy fibers. In the cerebellum, mossy fibers terminate in bands that are topographically aligned with stripes of Purkinje cells. While much is known about the molecular heterogeneity of Purkinje cell stripes, little is known about whether mossy fiber compartments have distinct molecular profiles. Here, we show that the vesicular glutamate transporters VGLUT1 and VGLUT2, which mediate glutamate uptake into synaptic vesicles of excitatory neurons, are expressed in complementary bands of mossy fibers in the adult mouse cerebellum. Using a combination of immunohistochemistry and anterograde tracing, we found heavy VGLUT2 and weak VGLUT1 expression in bands of spinocerebellar mossy fibers. The adjacent bands, which are in part comprised of dorsal column nuclei mossy fibers, strongly express VGLUT1 and weakly express VGLUT2. Simultaneous injections of fluorescent tracers into the dorsal column nuclei and lower thoracic-upper lumbar spinal cord revealed that upper and lower limb sensory pathways innervate adjacent VGLUT1/VGLUT2 parasagittal bands. In summary, we demonstrate that VGLUT1 and VGLUT2 are differentially expressed by dorsal column nuclei and spinocerebellar mossy fibers, which project to complementary cerebellar bands and respect common compartmental boundaries in the adult mouse cerebellum.
    No preview · Article · Aug 2011 · Brain Structure and Function
  • Stacey L Reeber · Roy V Sillitoe
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    ABSTRACT: The cerebellum (Cb) of mammals and birds consists of an evolutionarily conserved map defined by Purkinje cell (PC) protein expression. In mice, ZebrinII/aldolaseC is expressed in a striking array of stripes in lobules I-V (anterior zone; AZ) and VIII-anterior IX (posterior zone; PZ), whereas the small heat shock protein 25 (HSP25) is expressed in stripes in lobules VI-VII (central zone, CZ) and posterior IX-X (nodular zone, NZ). Little is known about whether molecularly defined afferent subsets terminate within specific PC stripes or whether their topography is conserved across species. Using immunohistochemistry, we demonstrate in adult mice and rats that cocaine- and amphetamine-regulated transcript (CART) expression can be used to partition sensory-motor projections into complex topographic maps. We found that in mice CART was expressed in climbing fiber bands that generally corresponded to the pattern of HSP25-expressing PCs in the CZ/NZ. In contrast, CART was expressed in climbing fiber bands in all four transverse zones of the rat Cb. Within the rat AZ/PZ, climbing fibers terminated selectively within the dendrites of ZebrinII-immunoreactive PCs. In additional experiments, we observed CART expression in loose clusters of spinocerebellar mossy fibers in the mouse AZ/PZ, whereas in rat CART immunoreactive mossy fibers terminated predominantly in the CZ/NZ. We conclude that, although the overall topography of CART-expressing afferents is restricted within a conserved map of PC stripes and transverse zones, their termination patterns also reflect species-specific compartmental features.
    No preview · Article · Jun 2011 · The Journal of Comparative Neurology
  • Stacey L Reeber · Samrawit A Gebre · Roy V Sillitoe
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    ABSTRACT: Neural circuits are organized into complex topographic maps. Although several neuroanatomical and genetic tools are available for studying circuit architecture, a limited number of methods exist for reliably revealing the global patterning of multiple topographic projections. Here we used wheat germ agglutinin (WGA) conjugated to Alexa 555 and 488 for dual color fluorescent mapping of parasagittal spinocerebellar topography in three dimensions. Using tissue section and wholemount imaging we show that WGA-Alexa tracers have three main characteristics that make them ideal tools for analyses of neural projection topography. First, the intense brightness of Alexa fluorophores allows multi-color imaging of patterned afferent projections in wholemount preparations. Second, WGA-Alexa tracers robustly label the entire trajectory of developing and adult projections. Third, long tracts such as the adult spinocerebellar tract can be traced in less than 6 h. Moreover, using WGA-Alexa tracers we resolved a level of complexity in the compartmentalized topography of the spinocerebellar projection map that has never before been appreciated. In summary, we introduce versatile tracers for rapidly labeling multiple topographic projections in three dimensions and uncover wiring complexities in the spinocerebellar map.
    No preview · Article · Mar 2011 · Brain Structure and Function
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    Stacey L Reeber · Zaven Kaprielian
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    ABSTRACT: In the developing nervous system, pathfinding axons navigate through a series of intermediate targets in order to form synaptic connections. Vertebrate spinal commissural axons extend toward and across the floor plate (FP), a key intermediate target located at the ventral midline (VM). Subsequently, post-crossing commissural axons grow either alongside or significant distances away from the floor plate (FP), but never re-cross the VM. Consistent with this behavior, post-crossing commissural axons lose responsiveness to the FP-associated chemoattractants, Netrin-1 and SHH, and gain responsiveness to Slits, which are potent midline repellents, in vitro. In addition, the results of several in vivo studies suggest that the upregulation of Slit-binding repulsive Robo receptors, Robo1/2, alters the responsiveness of decussated commissural axons to midline guidance cues. Nevertheless, in vertebrates, it is unclear whether Robo1/2 are the sole or major repellent receptors responsible for driving these commissural axons away from the VM and preventing their re-entry into the FP. We recently re-visited these issues in the chick spinal cord by assessing the consequences of manipulating Robo expression on commissural axons in ovo. Our findings suggest that, at least in chick embryos, the upregulation of repulsive Robos on post-crossing axons alters the responsiveness of these axons to midline repellents and facilitates their expulsion from, but is not likely to have a significant role in preventing their re-entry into the VM.
    Preview · Article · Aug 2009 · Cell adhesion & migration
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    ABSTRACT: In vertebrate embryos, most spinal commissural axons cross the ventral midline (VM) and project either alongside or significant distances away from the floor plate (FP). The upregulation of repulsive Robo1/2 receptors on postcrossing commissural axons, in mammals, presumably allows these axons to respond to the midline-associated repellents, Slit1-3, facilitating their expulsion from, and prohibiting their reentry into, the FP. Compelling data suggest that Robo3 represses Robo1/2 function on precrossing axons and that Robo1/2 inhibit attractive guidance receptors on postcrossing axons, thereby ensuring that decussated axons are selectively responsive to midline Slits. However, whether Robo1/2 expel decussated commissural axons from the VM and/or prevent their reentry into the FP has not been explicitly established in vivo. Furthermore, some commissural axons do not require Robo1/2 to elaborate appropriate contralateral projections in the mouse spinal cord. Here, we use unilateral in ovo electroporation together with Atoh1 and Neurog1 enhancer elements to visualize, and assess the consequences of manipulating Robo expression on, dl1 and dl2 chick commissural axons. In response to misexpressing a cytoplasmic truncation of Robo1 and/or Robo2, which should block all Robo-ligand interactions, postcrossing commissural axons extend alongside, but do not project away from or reenter the FP. In contrast, misexpression of full-length Robo2 prevents many commissural axons from crossing the VM. Together, these findings support key and selective in vivo roles for Robo receptors in presumably altering the responsiveness of decussated commissural axons and facilitating their expulsion from the VM within the chick spinal cord.
    Preview · Article · Sep 2008 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    Full-text · Article · Jul 2006 · Developmental Biology

Publication Stats

152 Citations
46.86 Total Impact Points


  • 2012-2014
    • Baylor College of Medicine
      • • Department of Neuroscience
      • • Department of Pathology & Immunology
      Houston, Texas, United States
  • 2013
    • Texas Children's Hospital
      Houston, Texas, United States
  • 2011-2012
    • Yeshiva University
      • Dominick P. Purpura Department of Neuroscience
      New York, New York, United States
  • 2006-2011
    • Albert Einstein College of Medicine
      • "Dominick P. Purpura" Department of Neuroscience
      New York City, New York, United States