Ian A Meinertzhagen

Dalhousie University, Halifax, Nova Scotia, Canada

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Publications (164)917.15 Total impact

  • Alberto Stolfi · Kerrianne Ryan · Ian A Meinertzhagen · Lionel Christiaen ·
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    ABSTRACT: The neural crest is an evolutionary novelty that fostered the emergence of vertebrate anatomical innovations such as the cranium and jaws. During embryonic development, multipotent neural crest cells are specified at the lateral borders of the neural plate before delaminating, migrating and differentiating into various cell types. In invertebrate chordates (cephalochordates and tunicates), neural plate border cells express conserved factors such as Msx, Snail and Pax3/7 and generate melanin-containing pigment cells, a derivative of the neural crest in vertebrates. However, invertebrate neural plate border cells have not been shown to generate homologues of other neural crest derivatives. Thus, proposed models of neural crest evolution postulate vertebrate-specific elaborations on an ancestral neural plate border program, through acquisition of migratory capabilities and the potential to generate several cell types. Here we show that a particular neuronal cell type in the tadpole larva of the tunicate Ciona intestinalis, the bipolar tail neuron, shares a set of features with neural-crest-derived spinal ganglia neurons in vertebrates. Bipolar tail neuron precursors derive from caudal neural plate border cells, delaminate and migrate along the paraxial mesoderm on either side of the neural tube, eventually differentiating into afferent neurons that form synaptic contacts with both epidermal sensory cells and motor neurons. We propose that the neural plate borders of the chordate ancestor already produced migratory peripheral neurons and pigment cells, and that the neural crest evolved through the acquisition of a multipotent progenitor regulatory state upstream of multiple, pre-existing neural plate border cell differentiation programs.
    Nature 11/2015; 527(7578). DOI:10.1038/nature15758 · 41.46 Impact Factor
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    ABSTRACT: We reconstructed the synaptic circuits of seven columns in the second neuropil or medulla behind the fly's compound eye. These neurons embody some of the most stereotyped circuits in one of the most miniaturized of animal brains. The reconstructions allow us, for the first time to our knowledge, to study variations between circuits in the medulla's neighboring columns. This variation in the number of synapses and the types of their synaptic partners has previously been little addressed because methods that visualize multiple circuits have not resolved detailed connections, and existing connectomic studies, which can see such connections, have not so far examined multiple reconstructions of the same circuit. Here, we address the omission by comparing the circuits common to all seven columns to assess variation in their connection strengths and the resultant rates of several different and distinct types of connection error. Error rates reveal that, overall, <1% of contacts are not part of a consensus circuit, and we classify those contacts that supplement (E+) or are missing from it (E-). Autapses, in which the same cell is both presynaptic and postsynaptic at the same synapse, are occasionally seen; two cells in particular, Dm9 and Mi1, form ≥20-fold more autapses than do other neurons. These results delimit the accuracy of developmental events that establish and normally maintain synaptic circuits with such precision, and thereby address the operation of such circuits. They also establish a precedent for error rates that will be required in the new science of connectomics.
    Proceedings of the National Academy of Sciences 10/2015; 112(44). DOI:10.1073/pnas.1509820112 · 9.67 Impact Factor
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    ABSTRACT: The promise of extracting connectomes and performing useful analysis on large electron microscopy (EM) datasets has been an elusive dream for many years. Tracing in even the smallest portions of neuropil requires copious human annotation, the rate-limiting step for generating a connectome. While a combination of improved imaging and automatic segmentation will lead to the analysis of increasingly large volumes, machines still fail to reach the quality of human tracers. Unfortunately, small errors in image segmentation can lead to catastrophic distortions of the connectome. In this paper, to analyze very large datasets, we explore different mechanisms that are less sensitive to errors in automation. Namely, we advocate and deploy extensive synapse detection on the entire antennal lobe (AL) neuropil in the brain of the fruit fly Drosophila, a region much larger than any densely annotated to date. The resulting synapse point cloud produced is invaluable for determining compartment boundaries in the AL and choosing specific regions for subsequent analysis. We introduce our methodology in this paper for region selection and show both manual and automatic synapse annotation results. Finally, we note the correspondence between image datasets obtained using the synaptic marker, antibody nc82, and our datasets enabling registration between light and EM image modalities.
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    ABSTRACT: Synaptic circuits for identified behaviors in the Drosophila brain have typically been considered from either a developmental or functional perspective without reference to how the circuits might have been inherited from ancestral forms. For example, two candidate pathways for ON- and OFF-edge motion detection in the visual system act via circuits that use respectively either T4 or T5, two cell types of the fourth neuropil, or lobula plate (LOP), that exhibit narrow-field direction-selective responses and provide input to wide-field tangential neurons. T4 or T5 both have four subtypes that terminate one each in the four strata of the LOP. Representatives are reported in a wide range of Diptera, and both cell types exhibit various similarities in: (1) the morphology of their dendritic arbors; (2) their four morphological and functional subtypes; (3) their cholinergic profile in Drosophila; (4) their input from the pathways of L3 cells in the first neuropil, or lamina (LA), and by one of a pair of LA cells, L1 (to the T4 pathway) and L2 (to the T5 pathway); and (5) their innervation by a single, wide-field contralateral tangential neuron from the central brain. Progenitors of both also express the gene atonal early in their proliferation from the inner anlage of the developing optic lobe, being alone among many other cell type progeny to do so. Yet T4 receives input in the second neuropil, or medulla (ME), and T5 in the third neuropil or lobula (LO). Here we suggest that these two cell types were originally one, that their ancestral cell population duplicated and split to innervate separate ME and LO neuropils, and that a fiber crossing-the internal chiasma-arose between the two neuropils. The split most plausibly occurred, we suggest, with the formation of the LO as a new neuropil that formed when it separated from its ancestral neuropil to leave the ME, suggesting additionally that ME input neurons to T4 and T5 may also have had a common origin.
    Frontiers in Neural Circuits 07/2015; 9:33. DOI:10.3389/fncir.2015.00033 · 3.60 Impact Factor
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    Tina Schwabe · Jolanta A Borycz · Ian A Meinertzhagen · Thomas R Clandinin ·
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    ABSTRACT: Background: Neuronal circuits in worms, flies, and mammals are organized so as to minimize wiring length for a functional number of synaptic connections, a phenomenon called wiring optimization. However, the molecular mechanisms that establish optimal wiring during development are unknown. We addressed this question by studying the role of N-cadherin in the development of optimally wired neurite fascicles in the peripheral visual system of Drosophila. Results: Photoreceptor axons surround the dendrites of their postsynaptic targets, called lamina cells, within a concentric fascicle called a cartridge. N-cadherin is expressed at higher levels in lamina cells than in photoreceptors, and all genetic manipulations that invert these relative differences displace lamina cells to the periphery and relocate photoreceptor axon terminals into the center. Conclusions: Differential expression of a single cadherin is both necessary and sufficient to determine cartridge structure because it positions the most-adhesive elements that make the most synapses at the core and the less-adhesive elements that make fewer synapses at the periphery. These results suggest a general model by which differential adhesion can be utilized to determine the relative positions of axons and dendrites to establish optimal wiring.
    Current Biology 05/2014; 24(12). DOI:10.1016/j.cub.2014.04.047 · 9.57 Impact Factor
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    ABSTRACT: In the fly's visual motion pathways, two cell types-T4 and T5-are the first known relay neurons to signal small-field direction-selective motion responses [1]. These cells then feed into large tangential cells that signal wide-field motion. Recent studies have identified two types of columnar neurons in the second neuropil, or medulla, that relay input to T4 from L1, the ON-channel neuron in the first neuropil, or lamina, thus providing a candidate substrate for the elementary motion detector (EMD) [2]. Interneurons relaying the OFF channel from L1's partner, L2, to T5 are so far not known, however. Here we report that multiple types of transmedulla (Tm) neurons provide unexpectedly complex inputs to T5 at their terminals in the third neuropil, or lobula. From the L2 pathway, single-column input comes from Tm1 and Tm2 and multiple-column input from Tm4 cells. Additional input to T5 comes from Tm9, the medulla target of a third lamina interneuron, L3, providing a candidate substrate for L3's combinatorial action with L2 [3]. Most numerous, Tm2 and Tm9's input synapses are spatially segregated on T5's dendritic arbor, providing candidate anatomical substrates for the two arms of a T5 EMD circuit; Tm1 and Tm2 provide a second. Transcript profiling indicates that T5 expresses both nicotinic and muscarinic cholinoceptors, qualifying T5 to receive cholinergic inputs from Tm9 and Tm2, which both express choline acetyltransferase (ChAT). We hypothesize that T5 computes small-field motion signals by integrating multiple cholinergic Tm inputs using nicotinic and muscarinic cholinoceptors.
    Current biology: CB 04/2014; 24(10). DOI:10.1016/j.cub.2014.03.051 · 9.57 Impact Factor
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    ABSTRACT: Each neuropil module, or cartridge, in the fly's lamina has a fixed complement of cells. Of five types of monopolar cell interneurons, only L4 has collaterals that invade neighboring cartridges. In the proximal lamina, these collaterals form reciprocal synapses with both the L2 of their own cartridge and the L4 collateral branches from two other neighboring cartridges. During synaptogenesis, L4 collaterals strongly express the cell adhesion protein Kirre, a member of the irre cell recognition module (IRM) group of proteins ( Fischbach et al., 2009 , J Neurogenet, 23, 48-67). The authors show by mutant analysis and gene knockdown techniques that L4 neurons develop their lamina collaterals in the absence of this cell adhesion protein. Using electron microscopy (EM), the authors demonstrate, however, that without Kirre protein these L4 collaterals selectively form fewer synapses. The collaterals of L4 neurons of various genotypes reconstructed from serial-section EM revealed that the number of postsynaptic sites was dramatically reduced in the absence of Kirre, almost eliminating any synaptic input to L4 neurons. A significant reduction of presynaptic sites was also detected in kirre(0) mutants and gene knockdown flies using RNA interference. L4 neuron reciprocal synapses are thus almost eliminated. A presynaptic marker, Brp-short(GFP) confirmed these data using confocal microscopy. This study reveals that removing Kirre protein specifically disrupts the functional L4 synaptic network in the Drosophila lamina.
    Journal of neurogenetics 04/2014; 28(3-4). DOI:10.3109/01677063.2014.883390 · 1.27 Impact Factor
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    ABSTRACT: The small GTPase Rab7 is a key regulator of endosomal maturation in eukaryotic cells. Mutations in rab7 are thought to cause the dominant neuropathy Charcot-Marie-Tooth 2B (CMT2B) by a gain-of-function mechanism. Here we show that loss of rab7, but not overexpression of rab7 CMT2B mutants, causes adult-onset neurodegeneration in a Drosophila model. All CMT2B mutant proteins retain 10–50% function based on quantitative imaging, electrophysiology, and rescue experiments in sensory and motor neurons in vivo. Consequently, expression of CMT2B mutants at levels between 0.5 and 10-fold their endogenous levels fully rescues the neuropathy-like phenotypes of the rab7 mutant. Live imaging reveals that CMT2B proteins are inefficiently recruited to endosomes, but do not impair endosomal maturation. These findings are not consistent with a gain-of-function mechanism. Instead, they indicate a dosage-dependent sensitivity of neurons to rab7-dependent degradation. Our results suggest a therapeutic approach opposite to the currently proposed reduction of mutant protein function. DOI: http://dx.doi.org/10.7554/eLife.01064.001
    eLife Sciences 12/2013; 2:e01064. DOI:10.7554/eLife.01064 · 9.32 Impact Factor
  • M Burrows · I A Meinertzhagen · P Bräunig ·
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    ABSTRACT: The planthopper insect Issus produces one of the fastest and most powerful jumps of any insect. The jump is powered by large muscles that are found in its thorax and that, in other insects, contribute to both flying and walking movements. These muscles were therefore analysed by transmission electron microscopy to determine whether they have the properties of fast-acting muscle used in flying or those of more slowly acting muscle used in walking. The muscle fibres are arranged in a parallel bundle that inserts onto an umbrella-shaped tendon. The individual fibres have a diameter of about 70 μm and are subdivided into myofibrils a few micrometres in diameter. No variation in ultrastructure was observed in various fibres taken from different parts of the muscle. The sarcomeres are about 15 μm long and the A bands about 10 μm long. The Z lines are poorly aligned within a myofibril. Mitochondrial profiles are sparse and are close to the Z lines. Each thick filament is surrounded by 10-12 thin filaments and the registration of these arrays of filaments is irregular. Synaptic boutons from the two excitatory motor neurons to the muscle fibres are characterised by accumulations of ~60 translucent 40-nm-diameter vesicle profiles per section, corresponding to an estimated 220 vesicles, within a 0.5-μm hemisphere at a presynaptic density. All ultrastructural features conform to those of slow muscle and thus suggest that the muscle is capable of slow sustained contractions in keeping with its known actions during jumping. A fast and powerful movement is thus generated by a slow muscle.
    Cell and Tissue Research 10/2013; 355(1). DOI:10.1007/s00441-013-1731-6 · 3.57 Impact Factor
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    ABSTRACT: Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in the insect visual system remains elusive. Here we develop a semi-automated pipeline using electron microscopy to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla. By matching reconstructed neurons to examples from light microscopy, we assigned neurons to cell types and assembled a connectome of the repeating module of the medulla. Within this module, we identified cell types constituting a motion detection circuit, and showed that the connections onto individual motion-sensitive neurons in this circuit were consistent with their direction selectivity. Our results identify cellular targets for future functional investigations, and demonstrate that connectomes can provide key insights into neuronal computations.
    Nature 08/2013; 500(7461):175-81. DOI:10.1038/nature12450 · 41.46 Impact Factor
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    ABSTRACT: The first Rabbit Retinal Connectome volume (RC1), constructed via automated transmission electron microscopy (ATEM) and computational molecular phenotyping (CMP), spans the mid-inner nuclear layer (INL) at section 001 to the ganglion cell layer (GCL) at section 371, shown in a mirror image below. RC1 is a short cylinder ≈ 250 μm in diameter and ≈ 30 μm high containing 341 ATEM sections and 11 intercalated CMP sections. The cylinder is capped at top and bottom with 10-section CMP series allowing molecular segmentation of cells, and an activity marker, 1-amino-4-guanidobutane (AGB), to mark cells differentially stimulated via glutamatergic synapses. ATEM section 001 is a horizontal plane section through the INL visualized with GABA.glycine.glutamate → red.green.blue transparency mapping and a dark gold alpha channel (ANDed taurine + glutamine channels). ATEM section 371 is a horizontal plane section through the GCL visualized with GABA.AGB.glutamate → red.green.blue transparency mapping.
    The Journal of Comparative Neurology 04/2013; 521(5). DOI:10.1002/cne.23244 · 3.23 Impact Factor
  • Kevin Luethy · Shilpa Rawal · Birgit Ahrens · Ian Meinertzhagen · KF Fischbach ·
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    ABSTRACT: Kirre (Kin-of-irre) is a Neph-like member of the evolutionarily conserved IRM protein family (1) with 5 extracellular Ig-domains, a single transmembrane domain and a cytoplasmic tail containing a PDZ-binding domain at its C-terminus. Our studies in Drosophila aim to secure an understanding of the neural function of this protein and we have chosen two paradigms for our investigations: the arborizations of L4 neurons in the optic lamina and the axon terminals of olfactory receptor neurons in the antennal lobe. L4 neurons are the only monopolar cells in each of the synaptic modules, or cartridges of the fly’s lamina that invade two neighboring cartridges via collateral neurites. These collaterals display strong -Kirre immunoreactivity in the proximal lamina, and there L4 neurons form reciprocal synapses with both L2 dendrites and the collaterals from neighbouring L4 neurons. Our light and electron microscopy has shown that the knockdown and knockout of Kirre in L4 neurons selectively reduces synapse numbers. This seems to result from specific defects in target recognition. We now try to generalize these results on target recognition and/or synaptogenesis by investigating Kirre function in the antennal lobes as well. Here olfactory receptor axons display strong -Kirre immunoreactivity. One of the questions we try to answer is whether heterophilic or homophilic trans interactions play a role in the effect of Kirre on synapse number. Homophilic interactions have been reported for Kirrel2 and Kirrel3 in the olfactory system of the mouse (2). Another question involves the degree of redundancy of Kirre with its paralogue Rst (Roughest, 1). Support: DFG Fi336/8-1 (to K-F.F.) and NIH 03592 (to I.A.M.)
    Neurofly, Padua; 12/2012
  • Ayami Matsushima · Kerrianne Ryan · Yasuyuki Shimohigashi · Ian A Meinertzhagen ·
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    ABSTRACT: Bisphenol A (BPA) is widely used industrially to produce polycarbonate plastics and epoxy resins. Numerous studies document the harmful effects caused by low-dose BPA exposure especially on nervous systems and behavior in experimental animals such as mice and rats. Here, we exposed embryos of a model chordate, Ciona intestinalis, to seawater containing BPA to evaluate adverse effects on embryonic development and on the swimming behavior of subsequent larvae. Ciona is ideal because its larva develops rapidly and has few cells. The rate of larval hatching decreased in a dose-dependent manner with exposures to BPA above 3 μM; swimming behavior was also affected in larvae emerging from embryos exposed to 1 μM BPA. Adverse effects were most severe on fertilized eggs exposed to BPA within 7 h post-fertilization. Ciona shares twelve nuclear receptors with mammals, and BPA is proposed to disturb the physiological functions of one or more of these.
    Environmental Pollution 11/2012; 173C:257-263. DOI:10.1016/j.envpol.2012.10.015 · 4.14 Impact Factor
  • Ian A Meinertzhagen · Chi-Hon Lee ·
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    ABSTRACT: Fly and vertebrate nervous systems share many organizational features, such as layers, columns and glomeruli, and utilize similar synaptic components, such as ion channels and receptors. Both also exhibit similar network features. Recent technological advances, especially in electron microscopy, now allow us to determine synaptic circuits and identify pathways cell-by-cell, as part of the fly's connectome. Genetic tools provide the means to identify synaptic components, as well as to record and manipulate neuronal activity, adding function to the connectome. This review discusses technical advances in these emerging areas of functional connectomics, offering prognoses in each and identifying the challenges in bridging structural connectomics to molecular biology and synaptic physiology, thereby determining fundamental mechanisms of neural computation that underlie behavior.
    Advances in genetics 10/2012; 80:99-151. DOI:10.1016/B978-0-12-404742-6.00003-X · 6.76 Impact Factor
  • Claudia Groh · Zhiyuan Lu · Ian A Meinertzhagen · Wolfgang Rössler ·
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    ABSTRACT: The mushroom bodies are high-order sensory integration centers in the insect brain. In the honeybee, their main sensory input regions are large, doubled calyces with modality-specific, distinct sensory neuropil regions. We investigated adult structural plasticity of input synapses in the microglomeruli of the olfactory lip and visual collar. Synapsin-immunolabeled whole-mount brains reveal that during the natural transition from nursing to foraging, a significant volume increase in the calycal subdivisions is accompanied by a decreased packing density of boutons from input projection neurons. To investigate the associated ultrastructural changes at pre- and postsynaptic sites of individual microglomeruli, we employed serial-section electron microscopy. In general, the membrane surface area of olfactory and visual projection neuron boutons increased significantly between 1-day-old bees and foragers. Both types of boutons formed ribbon and non-ribbon synapses. The percentage of ribbon synapses per bouton was significantly increased in the forager. At each presynaptic site the numbers of postsynaptic partners-mostly Kenyon cell dendrites-likewise increased. Ribbon as well as non-ribbon synapses formed mainly dyads in the 1-day-old bee, and triads in the forager. In the visual collar, outgrowing Kenyon cell dendrites form about 140 contacts upon a projection neuron bouton in the forager compared with only about 95 in the 1-day-old bee, resulting in an increased divergence ratio between the two stages. This difference suggests that synaptic changes in calycal microcircuits of the mushroom body during periods of altered sensory activity and experience promote behavioral plasticity underlying polyethism and social organization in honeybee colonies.
    The Journal of Comparative Neurology 10/2012; 520(15):3509-27. DOI:10.1002/cne.23102 · 3.23 Impact Factor
  • Ian A Meinertzhagen ·
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    ABSTRACT: No abstract is available for this article.
    The Journal of Comparative Neurology 08/2012; 520(12):2559-61. DOI:10.1002/cne.23136 · 3.23 Impact Factor
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    Nancy J Butcher · Anja B Friedrich · Zhiyuan Lu · Hiromu Tanimoto · Ian A Meinertzhagen ·
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    ABSTRACT: To investigate how sensory information is processed, transformed, and stored within an olfactory system, we examined the anatomy of the input region, the calyx, of the mushroom bodies of Drosophila melanogaster. These paired structures are important for various behaviors, including olfactory learning and memory. Cells in the input neuropil, the calyx, are organized into an array of microglomeruli each comprising the large synaptic bouton of a projection neuron (PN) from the antennal lobe surrounded by tiny postsynaptic neurites from intrinsic Kenyon cells. Extrinsic neurons of the mushroom body also contribute to the organization of microglomeruli. We employed a combination of genetic reporters to identify single cells in the Drosophila calyx by light microscopy and compared these with cell shapes, synapses, and circuits derived from serial-section electron microscopy. We identified three morphological types of PN boutons, unilobed, clustered, and elongated; defined three ultrastructural types, with clear- or dense-core vesicles and those with a dark cytoplasm having both; reconstructed diverse dendritic specializations of Kenyon cells; and identified Kenyon cell presynaptic sites upon extrinsic neurons. We also report new features of calyx synaptic organization, in particular extensive serial synapses that link calycal extrinsic neurons into a local network, and the numerical proportions of synaptic contacts between calycal neurons. All PN bouton types had more ribbon than nonribbon synapses, dark boutons particularly so, and ribbon synapses were larger and with more postsynaptic elements (2-14) than nonribbon (1-10). The numbers of elements were in direct proportion to presynaptic membrane area. Extrinsic neurons exclusively had ribbon synapses.
    The Journal of Comparative Neurology 07/2012; 520(10):2185-201. DOI:10.1002/cne.23037 · 3.23 Impact Factor
  • Tara N Edwards · Andrea C Nuschke · Aljoscha Nern · Ian A Meinertzhagen ·
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    ABSTRACT: The visual system of Drosophila is an excellent model for determining the interactions that direct the differentiation of the nervous system's many unique cell types. Glia are essential not only in the development of the nervous system, but also in the function of those neurons with which they become associated in the adult. Given their role in visual system development and adult function we need to both accurately and reliably identify the different subtypes of glia, and to relate the glial subtypes in the larval brain to those previously described for the adult. We viewed driver expression in subsets of larval eye disc glia through the earliest stages of pupal development to reveal the counterparts of these cells in the adult. Two populations of glia exist in the lamina, the first neuropil of the adult optic lobe: those that arise from precursors in the eye-disc/optic stalk and those that arise from precursors in the brain. In both cases, a single larval source gives rise to at least three different types of adult glia. Furthermore, analysis of glial cell types in the second neuropil, the medulla, has identified at least four types of astrocyte-like (reticular) glia. Our clarification of the lamina's adult glia and identification of their larval origins, particularly the respective eye disc and larval brain contributions, begin to define developmental interactions which establish the different subtypes of glia. J. Comp. Neurol. 520:2067-2085, 2012. © 2012 Wiley Periodicals, Inc.
    The Journal of Comparative Neurology 07/2012; 520(10):Spc1. DOI:10.1002/cne.23122 · 3.23 Impact Factor
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    ABSTRACT: Flies recycle the photoreceptor neurotransmitter histamine by conjugating it to β-alanine to form β-alanyl-histamine (carcinine). The conjugation is regulated by Ebony, while Tan hydrolyses carcinine, releasing histamine and β-alanine. In Drosophila, β-alanine synthesis occurs either from uracil or from the decarboxylation of aspartate but detailed roles for the enzymes responsible remain unclear. Immunohistochemically detected β-alanine is present throughout the fly's entire brain, and is enhanced in the retina especially in the pseudocone, pigment and photoreceptor cells of the ommatidia. HPLC determinations reveal 10.7 ng of β-alanine in the wild-type head, roughly five times more than histamine. When wild-type flies drink uracil their head β-alanine increases more than after drinking l-aspartic acid, indicating the effectiveness of the uracil pathway. Mutants of black, which lack aspartate decarboxylase, cannot synthesize β-alanine from l-aspartate but can still synthesize it efficiently from uracil. Our findings demonstrate a novel function for pigment cells, which not only screen ommatidia from stray light but also store and transport β-alanine and carcinine. This role is consistent with a β-alanine-dependent histamine recycling pathway occurring not only in the photoreceptor terminals in the lamina neuropile, where carcinine occurs in marginal glia, but vertically via a long pathway that involves the retina. The lamina's marginal glia are also a hub involved in the storage and/or disposal of carcinine and β-alanine.
    Journal of Experimental Biology 04/2012; 215(Pt 8):1399-411. DOI:10.1242/jeb.060699 · 2.90 Impact Factor
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    ABSTRACT: Soluble NSF attachment protein receptors (SNAREs) are the core proteins in membrane fusion. The neuron-specific synaptic v-SNARE n-syb (neuronal Synaptobrevin) plays a key role during synaptic vesicle exocytosis. In this paper, we report that loss of n-syb caused slow neurodegeneration independent of its role in neurotransmitter release in adult Drosophila melanogaster photoreceptor neurons. In addition to synaptic vesicles, n-Syb localized to endosomal vesicles. Loss of n-syb lead to endosomal accumulations, transmembrane protein degradation defects, and a secondary increase in autophagy. Our evidence suggests a primary defect of impaired delivery of vesicles that contain degradation proteins, including the acidification-activated Cathepsin proteases and the neuron-specific proton pump and V0 adenosine triphosphatase component V100. Overexpressing V100 partially rescued n-syb-dependent degeneration through an acidification-independent endosomal sorting mechanism. Collectively, these findings reveal a role for n-Syb in a neuron-specific sort-and-degrade mechanism that protects neurons from degeneration. Our findings further shed light on which intraneuronal compartments exhibit increased or decreased neurotoxicity.
    The Journal of Cell Biology 01/2012; 196(2):261-76. DOI:10.1083/jcb.201108088 · 9.83 Impact Factor

Publication Stats

8k Citations
917.15 Total Impact Points


  • 1980-2014
    • Dalhousie University
      • Department of Psychology and Neuroscience
      Halifax, Nova Scotia, Canada
  • 2013
    • University of Utah
      • John Moran Eye Center
      Salt Lake City, UT, United States
  • 2012
    • Life Science Research Center
      Halifax, Nova Scotia, Canada
  • 1993
    • Jagiellonian University
      • Institute of Zoology
      Cracovia, Lesser Poland Voivodeship, Poland
  • 1983
    • Marine Biological Laboratory
      Falmouth, Massachusetts, United States
  • 1977
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1970-1972
    • Australian National University
      Canberra, Australian Capital Territory, Australia