Carol A Mason

Columbia University, New York City, New York, United States

Are you Carol A Mason?

Claim your profile

Publications (48)431.33 Total impact

  • Source
  • Marian Joëls, Carol Mason
    [Show abstract] [Hide abstract]
    ABSTRACT: This year marks the first time that the largest Neuroscience societies in the U.S. and Europe are led by females. Here we discuss the challenges that women face in moving through the ranks of academia and propose ways to increase women's representation in the field.
    Neuron 06/2014; 82(6):1196-1199. · 15.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Proper binocular vision depends on the routing at the optic chiasm of the correct proportion of retinal ganglion cell (RGC) axons that project to the same (ipsilateral) and opposite (contralateral) side of the brain. The ipsilateral RGC projection is reduced in mammals with albinism, a congenital disorder characterized by deficient pigmentation in the skin, hair, and eyes. Compared to the pigmented embryonic mouse retina, the albino embryonic mouse retina has fewer RGCs that express the zinc-finger transcription factor, Zic2, which is transiently expressed by RGCs fated to project ipsilaterally. Here, using Zic2 as a marker of ipsilateral RGCs, Islet2 as a marker of contralateral RGCs, and birthdating, we investigate spatiotemporal dynamics of RGC production as they relate to the phenotype of diminished ipsilateral RGC number in the albino retina.
    Neural Development 05/2014; 9(1):11. · 3.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thalamus is a potent driver of cortical activity even though cortical synapses onto excitatory layer 4 neurons outnumber thalamic synapses 10 to 1. Previous in vitro studies have proposed that thalamocortical (TC) synapses are stronger than corticocortical (CC) synapses. Here, we investigated possible anatomical and physiological differences between these inputs in the rat in vivo. We developed a high-throughput light microscopy method, validated by electron microscopy, to completely map the locations of synapses across an entire dendritic tree. This demonstrated that TC synapses are slightly more proximal to the soma than CC synapses, but detailed compartmental modeling predicted that dendritic filtering does not appreciably favor one synaptic class over another. Measurements of synaptic strength in intact animals confirmed that both TC and CC synapses are weak and approximately equivalent. We conclude that thalamic effectiveness does not rely on enhanced TC strength, but rather on coincident activation of converging inputs.
    Journal of Neuroscience 05/2014; 34(20):6746-58. · 6.91 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We describe a clearing method for enhanced visualization of cell morphology and connections in neuronal and non-neuronal tissue. Using Clear(T) or Clear(T2), which are composed of formamide or formamide/polyethylene glycol, respectively, embryos, whole mounts and thick brain sections can be rapidly cleared with minimal volume changes. Unlike other available clearing techniques, these methods do not use detergents or solvents, and thus preserve lipophilic dyes, fluorescent tracers and immunohistochemical labeling, as well as fluorescent-protein labeling.
    Development 03/2013; 140(6):1364-8. · 6.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The absence or deficiency of melanin as in albinos, has detrimental effects on retinal development that include aberrant axonal projections from eye to brain and impaired vision. In pigmented retinal pigment epithelium (RPE), dihydroxyphenalanine (L-Dopa), an intermediate in the synthetic path for melanin, has been hypothesized to regulate the tempo of neurogenesis. The time course of expression of retinal L-Dopa, whether it is harbored exclusively in the RPE, the extent of deficiency in albinos compared to isogenic controls, and whether L-Dopa can be restored if exogenously delivered to the albino have been unknown. METHODOLOGYPRINCIPAL FINDINGS: L-Dopa and catecholamines including dopamine extracted from retinas of pigmented (C57BL/6J) and congenic albino (C57BL/6J-tyr(c2j) ) mice, were measured throughout development beginning at E10.5 and at maturity. L-Dopa, but not dopamine nor any other catecholamine, appears in pigmented retina as soon as tyrosinase is expressed in RPE at E10.5. In pigmented retina, L-Dopa content increases throughout pre- and postnatal development until the end of the first postnatal month after which it declines sharply. This time course reflects the onset and completion of retinal development. L-Dopa is absent from embryonic albino retina and is greatly reduced in postnatal albino retina compared to pigmented retina. Dopamine is undetectable in both albino and pigmented retinas until after the postnatal expression of the neuronal enzyme tyrosine hydroxylase. If provided to pregnant albino mothers, L-Dopa accumulates in the RPE of the fetuses. CONCLUSIONS: L-Dopa in pigmented RPE is most abundant during development after which content declines. This L-Dopa is not converted to dopamine. L-Dopa is absent or at low levels in albino retina and can be restored to the RPE by administration in utero. These findings further implicate L-Dopa as a factor in the RPE that could influence development, and demonstrate that administration of L-Dopa could be a means to rescue developmental abnormalities characteristic of albinos.
    PLoS ONE 01/2013; 8(3):e57184. · 3.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: At the optic chiasm, retinal ganglion cells (RGCs) project ipsi- or contralaterally to establish the circuitry for binocular vision. Ipsilateral guidance programs have been characterized, but contralateral guidance programs are not well understood. Here, we identify a tripartite molecular system for contralateral RGC projections: Semaphorin6D (Sema6D) and Nr-CAM are expressed on midline radial glia and Plexin-A1 on chiasm neurons, and Plexin-A1 and Nr-CAM are also expressed on contralateral RGCs. Sema6D is repulsive to contralateral RGCs, but Sema6D in combination with Nr-CAM and Plexin-A1 converts repulsion to growth promotion. Nr-CAM functions as a receptor for Sema6D. Sema6D, Plexin-A1, and Nr-CAM are all required for efficient RGC decussation at the optic chiasm. These findings suggest a mechanism by which a complex of Sema6D, Nr-CAM, and Plexin-A1 at the chiasm midline alters the sign of Sema6D and signals Nr-CAM/Plexin-A1 receptors on RGCs to implement the contralateral RGC projection.
    Neuron 05/2012; 74(4):676-90. · 15.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The divergence of retinal ganglion cell (RGC) axons into ipsilateral and contralateral projections at the optic chiasm and the subsequent segregation of retinal inputs into eye-specific domains in their target, the dorsal lateral geniculate nucleus (dLGN), are crucial for binocular vision. In albinism, affected individuals exhibit a lack or reduction of pigmentation in the eye and skin, a concomitant reduced ipsilateral projection, and diverse visual defects. Here we investigate how such altered decussation affects eye-specific retinogeniculate targeting in albino mice using the C57BL/6 Tyr(c-2J/c-2J) strain, in which tyrosinase, necessary for melanogenesis, is mutated. In albino mice, fewer RGCs from the ventrotemporal (VT) retina project ipsilaterally, reflected in a decrease in cells expressing ipsilateral markers. In addition, a population of RGCs from the VT retina projects contralaterally and, within the dLGN, their axons cluster into a patch separated from the contralateral termination area. Furthermore, eye-specific segregation is not complete in the albino dLGN and, upon perturbing postnatal retinal activity with epibatidine, the ipsilateral projection fragments and the aberrant contralateral patch disappears. These results suggest that the defects in afferent targeting and activity-dependent refinement in the albino dLGN arise from RGC misspecification together with potential perturbations of early activity patterns in the albino retina.
    Journal of Neuroscience 04/2012; 32(14):4821-6. · 6.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dendrites achieve characteristic spacing patterns during development to ensure appropriate coverage of territories. Mechanisms of dendrite positioning via repulsive dendrite-dendrite interactions are beginning to be elucidated, but the control, and importance, of dendrite positioning relative to their substrate is poorly understood. We found that dendritic branches of Drosophila dendritic arborization sensory neurons can be positioned either at the basal surface of epidermal cells, or enclosed within epidermal invaginations. We show that integrins control dendrite positioning on or within the epidermis in a cell autonomous manner by promoting dendritic retention on the basal surface. Loss of integrin function in neurons resulted in excessive self-crossing and dendrite maintenance defects, the former indicating a role for substrate interactions in self-avoidance. In contrast to a contact-mediated mechanism, we find that integrins prevent crossings that are noncontacting between dendrites in different three-dimensional positions, revealing a requirement for combined dendrite-dendrite and dendrite-substrate interactions in self-avoidance.
    Neuron 01/2012; 73(1):79-91. · 15.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dendrites achieve characteristic spacing patterns during development to ensure appropriate coverage of territories. Mechanisms of dendrite positioning via repulsive dendrite-dendrite interactions are beginning to be elucidated, but the control, and importance, of dendrite positioning relative to their substrate is poorly understood. We found that dendritic branches of Drosophila dendritic arborization sensory neurons can be positioned either at the basal surface of epidermal cells, or enclosed within epidermal invaginations. We show that integrins control dendrite positioning on or within the epidermis in a cell autonomous manner by promoting dendritic retention on the basal surface. Loss of integrin function in neurons resulted in excessive self-crossing and dendrite maintenance defects, the former indicating a role for substrate interactions in self-avoidance. In contrast to a contact-mediated mechanism, we find that integrins prevent crossings that are noncontacting between dendrites in different three-dimensional positions, revealing a requirement for combined dendrite-dendrite and dendrite-substrate interactions in self-avoidance.
    Neuron 01/2012; 73(1-73):79-91. · 15.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Carefully designed animal models of genetic risk factors are likely to aid our understanding of the pathogenesis of schizophrenia. Here, we study a mouse strain with a truncating lesion in the endogenous Disc1 ortholog designed to model the effects of a schizophrenia-predisposing mutation and offer a detailed account of the consequences that this mutation has on the development and function of a hippocampal circuit. We uncover widespread and cumulative cytoarchitectural alterations in the dentate gyrus during neonatal and adult neurogenesis, which include errors in axonal targeting and are accompanied by changes in short-term plasticity at the mossy fiber/CA3 circuit. We also provide evidence that cAMP levels are elevated as a result of the Disc1 mutation, leading to altered axonal targeting and dendritic growth. The identified structural alterations are, for the most part, not consistent with the growth-promoting and premature maturation effects inferred from previous RNAi-based Disc1 knockdown. Our results provide support to the notion that modest disturbances of neuronal connectivity and accompanying deficits in short-term synaptic dynamics is a general feature of schizophrenia-predisposing mutations.
    Proceedings of the National Academy of Sciences 11/2011; 108(49):E1349-58. · 9.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Precise regulation of neuroprogenitor cell proliferation and differentiation is required for successful brain development, but the factors that contribute to this are only incompletely understood. The transcription factor ATF5 promotes proliferation of cerebral cortical neuroprogenitor cells and its down regulation permits their differentiation. Here, we examine the expression and regulation of ATF5 in cerebellar granule neuron progenitor cells (CGNPs) as well as the role of ATF5 in the transition of CGNPs to postmitotic cerebellar granule neurons (GCNs). We find that ATF5 is expressed by proliferating CGNPs in both the embryonic and postnatal cerebellar external granule layer (EGL) and in the rhombic lip, the embryonic structure from which the EGL arises. In contrast, ATF5 is undetectable in postmitotic GCNs. In highly enriched dissociated cultures of CGNPs and CGNs, ATF5 is expressed only in CGNPs. Constitutive ATF5 expression in CGNPs does not affect their proliferation or exit from the cell cycle. In contrast, in presence of sonic hedgehog (Shh), a mitogen for CGNPs, constitutively expressed ATF5 promotes CGNP proliferation and delays their cell cycle exit and differentiation. Conversely, ATF5 loss-of-function conferred by a dominant-negative form of ATF5 significantly diminishes Shh-stimulated CGNP proliferation and promotes differentiation. In parallel with its stimulation of CGNP proliferation, Shh enhances ATF5 expression by what appeared to be a posttranscriptional mechanism involving protein stabilization. These findings indicate a reciprocal interaction between ATF5 and Shh in which Shh stimulates ATF5 expression and in which ATF5 contributes to Shh-stimulated CGNP expansion.
    Developmental Neurobiology 09/2011; 72(6):789-804. · 4.42 Impact Factor
  • Source
    Alexandra Rebsam, Carol A Mason
    [Show abstract] [Hide abstract]
    ABSTRACT: Cadherins implement afferent-target matching in invertebrates, but proof for this concept in mammalian circuits has remained elusive. Two new studies in this issue of Neuron show that cadherin-6 mediates retinal ganglion cell target selection and that cadherin-9 promotes synapse specificity in the hippocampus.
    Neuron 08/2011; 71(4):566-8. · 15.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The function of neuronal networks relies on selective assembly of synaptic connections during development. We examined how synaptic specificity emerges in the pontocerebellar projection. Analysis of axon-target interactions with correlated light-electron microscopy revealed that developing pontine mossy fibers elaborate extensive cell-cell contacts and synaptic connections with Purkinje cells, an inappropriate target. Subsequently, mossy fiber-Purkinje cell connections are eliminated resulting in granule cell-specific mossy fiber connectivity as observed in mature cerebellar circuits. Formation of mossy fiber-Purkinje cell contacts is negatively regulated by Purkinje cell-derived BMP4. BMP4 limits mossy fiber growth in vitro and Purkinje cell-specific ablation of BMP4 in mice results in exuberant mossy fiber-Purkinje cell interactions. These findings demonstrate that synaptic specificity in the pontocerebellar projection is achieved through a stepwise mechanism that entails transient innervation of Purkinje cells, followed by synapse elimination. Moreover, this work establishes BMP4 as a retrograde signal that regulates the axon-target interactions during development.
    PLoS Biology 01/2011; 9(2):e1001013. · 12.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The circuit for binocular vision and stereopsis is established at the optic chiasm, where retinal ganglion cell (RGC) axons diverge into the ipsilateral and contralateral optic tracts. In the mouse retina, ventrotemporal (VT) RGCs express the guidance receptor EphB1, which interacts with the repulsive guidance cue ephrin-B2 on radial glia at the optic chiasm to direct VT RGC axons ipsilaterally. RGCs in the ventral retina also express EphB2, which interacts with ephrin-B2, whereas dorsal RGCs express low levels of EphB receptors. To investigate how growth cones of RGCs from different retinal regions respond upon initial contact with ephrin-B2, we utilized time-lapse imaging to characterize the effects of ephrin-B2 on growth cone collapse and axon retraction in real time. We demonstrate that bath application of ephrin-B2 induces rapid and sustained growth cone collapse and axon retraction in VT RGC axons, whereas contralaterally-projecting dorsotemporal RGCs display moderate growth cone collapse and little axon retraction. Dose response curves reveal that contralaterally-projecting ventronasal axons are less sensitive to ephrin-B2 treatment compared to VT axons. Additionally, we uncovered a specific role for Rho kinase signaling in the retraction of VT RGC axons but not in growth cone collapse. The detailed characterization of growth cone behavior in this study comprises an assay for the study of Eph signaling in RGCs, and provides insight into the phenomena of growth cone collapse and axon retraction in general.
    Developmental Neurobiology 09/2010; 70(11):781-94. · 4.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Partial decussation of sensory pathways allows neural inputs from both sides of the body to project to the same target region where these signals will be integrated. Here, to better understand mechanisms of eye-specific targeting, we studied how retinal ganglion cell (RGC) axons terminate in their thalamic target, the dorsal lateral geniculate nucleus (dLGN), when crossing at the optic chiasm midline is altered. In models with gain- and loss-of-function of EphB1, the receptor that directs the ipsilateral projection at the optic chiasm, misrouted RGCs target the appropriate retinotopic zone in the opposite dLGN. However, in EphB1(-/-) mice, the misrouted axons do not intermingle with normally projecting RGC axons and segregate instead into a distinct patch. We also revisited the role of retinal activity on eye-specific targeting by blocking correlated waves of activity with epibatidine into both eyes. We show that, in wild-type mice, retinal waves are necessary during the first postnatal week for both proper distribution and eye-specific segregation of ipsilateral axons in the mature dLGN. Moreover, in EphB1(-/-) mice, refinement of ipsilateral axons is perturbed in control conditions and is further impaired after epibatidine treatment. Finally, retinal waves are required for the formation of the segregated patch of misrouted axons in EphB1(-/-) mice. These findings implicate molecular determinants for targeting of eye-specific zones that are independent of midline guidance cues and that function in concert with correlated retinal activity to sculpt retinogeniculate projections.
    Journal of Neuroscience 11/2009; 29(47):14855-63. · 6.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: At the optic chiasm, retinal ganglion cell (RGC) axons make the decision to either avoid or traverse the midline, a maneuver that establishes the binocular pathways. In mice, the ipsilateral retinal projection arises from RGCs in the peripheral ventrotemporal (VT) crescent of the retina. These RGCs express the guidance receptor EphB1, which interacts with ephrin-B2 on radial glia cells at the optic chiasm to repulse VT axons away from the midline and into the ipsilateral optic tract. However, because VT RGCs express more than one EphB receptor, the sufficiency and specificity of the EphB1 receptor in directing the ipsilateral projection is unclear. In this study, we use in utero retinal electroporation to demonstrate that ectopic EphB1 expression can redirect RGCs with a normally crossed projection to an ipsilateral trajectory. Moreover, EphB1 is specifically required for rerouting RGC projections ipsilaterally, because introduction of the highly similar EphB2 receptor is much less efficient in redirecting RGC fibers, even when expressed at higher surface levels. Introduction of EphB1-EphB2 chimeric receptors into RGCs reveals that both extracellular and juxtamembrane domains of EphB1 are required to efficiently convert RGC projections ipsilaterally. Together, these data describe for the first time functional differences between two highly similar Eph receptors at a decision point in vivo, with EphB1 displaying unique properties that efficiently drives the uncrossed retinal projection.
    Journal of Neuroscience 04/2009; 29(11):3463-74. · 6.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The cerebellar cortex is a well described structure that provides unique opportunities for studying neuronal properties and development. Of the cerebellar neuronal types (granule cells, Purkinje cells and inhibitory interneurons), granule neurons are by far the most numerous and are the most abundant type of neurons in the mammalian brain. In rodents, cerebellar granule neurons are generated during the first two post-natal weeks from progenitor cells in the outermost layer of the cerebellar cortex, the external granule layer (EGL). The protocol presented here describes techniques to enrich and culture granule neurons and their progenitor cells from post-natal mouse cerebellum. We will describe procedures to obtain cultures of increasing purity which can be used to study the differentiation of proliferating progenitor cells into granule neurons. Once the progenitor cells differentiate, the cultures also provide a homogenous population of granule neurons for experimental manipulation and characterization of phenomena such as synaptogenesis, glutamate receptor function, interaction with other purified cerebellar cells or cell death.
    Journal of Visualized Experiments 02/2009;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The retina and its sole output neuron, the retinal ganglion cell (RGC), comprise an excellent model in which to examine biological questions such as cell differentiation, axon guidance, retinotopic organization and synapse formation. One drawback is the inability to efficiently and reliably manipulate gene expression in RGCs in vivo, especially in the otherwise accessible murine visual pathways. Transgenic mice can be used to manipulate gene expression, but this approach is often expensive, time consuming, and can produce unwanted side effects. In chick, in ovo electroporation is used to manipulate gene expression in RGCs for examining retina and RGC development. Although similar electroporation techniques have been developed in neonatal mouse pups, adult rats, and embryonic murine retinae in vitro, none of these strategies allow full characterization of RGC development and axon projections in vivo. To this end, we have developed two applications of electroporation, one in utero and the other ex vivo, to specifically target embryonic murine RGCs. With in utero retinal electroporation, we can misexpress or downregulate specific genes in RGCs and follow their axon projections through the visual pathways in vivo, allowing examination of guidance decisions at intermediate targets, such as the optic chiasm, or at target regions, such as the lateral geniculate nucleus. Perturbing gene expression in a subset of RGCs in an otherwise wild-type background facilitates an understanding of gene function throughout the retinal pathway. Additionally, we have developed a companion technique for analyzing RGC axon growth in vitro. We electroporate embryonic heads ex vivo, collect and incubate the whole retina, then prepare explants from these retinae several days later. Retinal explants can be used in a variety of in vitro assays in order to examine the response of electroporated RGC axons to guidance cues or other factors. In sum, this set of techniques enhances our ability to misexpress or downregulate genes in RGCs and should greatly aid studies examining RGC development and axon projections.
    Journal of Visualized Experiments 01/2009;

Publication Stats

2k Citations
431.33 Total Impact Points

Institutions

  • 2001–2014
    • Columbia University
      • • Department of Pathology & Cell Biology
      • • Center for Neurobiology and Behavior
      New York City, New York, United States
  • 2013
    • Tufts University
      Georgia, United States
  • 2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • CUNY Graduate Center
      New York City, New York, United States
  • 2003
    • Brown University
      • Department of Neuroscience
      Providence, RI, United States