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Reconstruction of neuronal activity and connectivity patterns in the zebrafish olfactory bulb

By Adrian A. Wanner


In the olfactory bulb (OB), odors evoke distributed patterns of activity across glomeruli that are reorganized by networks of interneurons (INs). This reorganization results in multiple computations including a decorrelation of activity patterns across the output neurons, the mitral cells (MCs). To understand the mechanistic basis of these computations it is essential to analyze the relationship between function and structure of the underlying circuit.\ud I combined in vivo twophoton calcium imaging with dense circuit reconstruction from complete serial block-face electron microscopy (SBEM) stacks of the larval zebrafish OB (4.5 dpf) with a voxel size of 9x9x25nm. To address bottlenecks in the workflow of SBEM, I developed a novel embedding and staining procedure that effectively reduces surface charging in SBEM and enables to acquire SBEM stacks with at least a ten-fold increase in both, signal-to-noise as well as acquisition speed.\ud I set up a high throughput neuron reconstruction pipeline with >30 professional tracers that is available for the scientific community (ariadne-service.com). To assure efficient and accurate circuit reconstruction, I developed PyKNOSSOS, a Python software for skeleton tracing and synapse annotation, and CORE, a skeleton consolidation procedure that combines redundant reconstruction with targeted expert input.\ud Using these procedures I reconstructed all neurons (>1000) in the larval OB. Unlike in the adult OB, INs were rare and appeared to represent specific subtypes, indicating that different sub-circuits develop sequentially. MCs were uniglomerular whereas inter-glomerular projections of INs were complex and biased towards groups of glomeruli that receive input from common types of sensory neurons. Hence, the IN network in the OB exhibits a topological organization that is governed by glomerular identity.\ud Calcium imaging revealed that the larval OB circuitry already decorrelates activity patterns evoked by similar odors. The comparison of inter-glomerular connectivity to the functional interactions between glomeruli indicates that pattern decorrelation depends on specific, non-random inter-glomerular IN projections. Hence, the topology of IN networks in the OB appears to be an important determinant of circuit function

Year: 2016
DOI identifier: 10.5451/unibas-006621634
OAI identifier: oai:edoc.unibas.ch:43341
Provided by: edoc

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  4. (1999). A systems perspective on early olfactory coding."
  5. (1969). A theory of cerebellar cortex."
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  7. (2012). Aberration-free three-dimensional multiphoton imaging of neuronal activity at kHz rates."
  8. (2008). Activity-dependent gating of lateral inhibition in the mouse olfactory bulb."
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  10. (2002). Amino acid odorants stimulate microvillar sensory neurons."
  11. (2004). Analyzing neural responses to natural signals: maximally informative dimensions."
  12. (2013). Analyzing the structure and function of neuronal circuits in zebrafish."
  13. (2010). As-rigid-as-possible mosaicking and serial section registration of large ssTEM datasets."
  14. (1990). Associative memory function in piriform (olfactory) cortex: computational modeling and neuropharmacology."
  15. (1996). Asynchronous onset of odorant receptor expression in the developing zebrafish olfactory system."
  16. (2013). Automated in-chamber specimen coating for serial block-face electron microscopy."
  17. (2006). Automating the collection of ultrathin serial sections for large volume TEM reconstructions."
  18. (1999). Beam-gas and signal-gas interactions in the variable pressure scanning electron microscope."
  19. (2004). Behavioral responses of newly hatched zebrafish (Danio rerio) to amino acid chemostimulants."
  20. (2012). Beyond the connectome: how neuromodulators shape neural circuits."
  21. (2012). Brainwide neuronal dynamics during motor adaptation in zebrafish."
  22. (1999). Catastrophic forgetting in connectionist networks."
  23. (2009). CATMAID: collaborative annotation toolkit for massive amounts of image data."
  24. (2013). Cellular-resolution connectomics: challenges of dense neural circuit reconstruction."
  25. (2015). Challenges of microtome-based serial blockface scanning electron microscopy in neuroscience."
  26. (2010). Circuit neuroscience in zebrafish."
  27. (2006). Coding and synaptic processing of sensory information in the glomerular layer of the olfactory bulb."
  28. (1997). Combinatorial and chemotopic odorant coding in the
  29. (2008). Computation of rotation minimizing frames."
  30. (2013). Computational identification of receptive fields."
  31. (2013). Connectomic reconstruction of the inner plexiform layer in the mouse retina."
  32. (2013). Controlling FIB-SBEM slice thickness by monitoring the transmitted ion beam."
  33. (2007). Correlation between neural spike trains increases with firing rate."
  34. (2003). Correlation between olfactory receptor cell type and function in the channel catfish."
  35. (1998). Cortex: statistics and geometry of neuronal connectivity.
  36. (2011). Cortical processing of odor objects."
  37. (2015). Deep learning in neural networks: an overview."
  38. (2015). Deep learning."
  39. (2016). Dense EM-based reconstruction of the interglomerular projectome in the zebrafish olfactory bulb."
  40. (2007). Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network."
  41. (2011). Digital scanned laser light-sheet fluorescence microscopy (DSLM) of zebrafish and Drosophila embryonic development." Cold Spring Harb Protoc
  42. (2008). Distinct deep short-axon cell subtypes of the main olfactory bulb provide novel intrabulbar and extrabulbar GABAergic connections."
  43. (2004). Distinctive image features from scale-invariant keypoints."
  44. (2012). Distribution and functional organization of glomeruli in the olfactory bulbs of zebrafish (Danio rerio)."
  45. (2010). Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe."
  46. (2005). Diversity in the olfactory epithelium of bony fishes: development, lamellar arrangement, sensory neuron cell types and transduction components."
  47. (2010). Divisive normalization in olfactory population codes."
  48. (2012). Dopaminergic modulation of mitral cells and odor responses in the zebrafish olfactory bulb."
  49. (2005). Early development of functional spatial maps in the zebrafish olfactory bulb."
  50. (2006). Early events in olfactory processing."
  51. (2007). Early functional development of interneurons in the zebrafish olfactory bulb."
  52. (2002). Efficient coding of natural sounds."
  53. (1994). Emerging principles of molecular signal processing by mitral/tufted cells in the olfactory bulb."
  54. (2013). Engineering approaches to illuminating brain structure and dynamics."
  55. (2010). Enhancing serial block-face scanning electron microscopy to enable high resolution 3D nanohistology of cells and tissues."
  56. (2010). Ephus: multipurpose data acquisition software for neuroscience experiments."
  57. (2013). Equalization of odor representations by a network of electrically coupled inhibitory interneurons."
  58. (2009). Evolutionary dynamics of olfactory receptor genes in chordates: interaction between environments and genomic contents."
  59. (2013). Experiencedependent versus experience-independent postembryonic development of distinct groups of zebrafish olfactory glomeruli."
  60. (2015). Extracellular space preservation aids the connectomic analysis of neural circuits."
  61. (2009). Extraordinary diversity of chemosensory receptor gene repertoires among vertebrates."
  62. (2009). From the olfactory bulb to higher brain centers: genetic visualization of secondary olfactory pathways in zebrafish."
  63. (2010). Fully automatic stitching and distortion correction of transmission electron microscope images."
  64. (2013). Functional development of the olfactory system in
  65. (2013). Functional development of the olfactory system in zebrafish."
  66. (2007). Generation and long-term persistence of new neurons in the adult zebrafish brain: a quantitative analysis."
  67. (2008). Genetic dissection of neural circuits."
  68. (2012). Genetically encoded optical indicators for the analysis of neuronal circuits."
  69. (2007). Hierarchical regulation of odorant receptor gene choice and subsequent axonal projection of olfactory sensory neurons in zebrafish."
  70. (1997). High School, focus in Natural Sciences, Lucerne, Switzerland
  71. (2011). High-accuracy neurite reconstruction for highthroughput neuroanatomy."
  72. (2012). High-contrast en bloc staining of neuronal tissue for field emission scanning electron microscopy."
  73. (2012). High-resolution optical control of spatiotemporal neuronal activity patterns in zebrafish using a digital micromirror device."
  74. (2015). High-resolution whole-brain staining for electron microscopic circuit reconstruction."
  75. (2015). High-resolution, highthroughput imaging with a multibeam scanning electron microscope."
  76. How much the eye tells the brain."
  77. (2001). How the olfactory system makes sense of scents."
  78. (2011). Ilastik: Interactive learning and segmentation toolkit.
  79. (2014). Imaging ATUM ultrathin section libraries with WaferMapper: a multi-scale approach to EM reconstruction of neural circuits."
  80. (2006). Imaging cellular signals in the heart in vivo: Cardiac expression of the high-signal Ca2+ indicator GCaMP2."
  81. (2011). Imaging in Neuroscience:
  82. (2008). Imaging in vivo: watching the brain in action."
  83. (1996). Imaging the functional organization of zebrafish hindbrain segments during escape behaviors."
  84. (2003). In vivo" monitoring of neuronal network activity in zebrafish by two-photon Ca(2+) imaging."
  85. (2013). Information processing in the olfactory system of zebrafish."
  86. (2005). Isolation and characterization of the laure olfactory behavioral mutant in the zebrafish, Danio rerio."
  87. (2012). Korsching
  88. (2015). Large-volume en-bloc staining for electron microscopy-based connectomics."
  89. (1979). Lead asparate, an en bloc contrast stain particularly useful for ultrastructural enzymology."
  90. (2014). Mapping neural connections."
  91. (1952). Measurement of current-voltage relations in the membrane of the giant axon of Loligo."
  92. (2001). Mechanisms governing dendritic gamma-aminobutyric acid (GABA) release in the rat olfactory bulb."
  93. (2010). Mechanisms of pattern decorrelation by recurrent neuronal circuits."
  94. (2009). Molecular genetic dissection of the zebrafish olfactory system."
  95. (2010). Molecular identity of periglomerular and short axon cells."
  96. (2008). Multiple functions of GABA A and GABA B receptors during pattern processing in the zebrafish olfactory bulb."
  97. (2004). Multiplexing using synchrony in the zebrafish olfactory bulb."
  98. (2005). Mutually exclusive glomerular innervation by two distinct types of olfactory sensory neurons revealed in transgenic zebrafish."
  99. (2011). Network anatomy and in vivo physiology of visual cortical neurons."
  100. (2013). Neural circuits mediating olfactory-driven behavior in fish."
  101. (2003). Neurodevelopmental defects in zebrafish (Danio rerio) at environmentally relevant dioxin (TCDD) concentrations."
  102. (1990). Neuronal architecture of the antennal lobe in Drosophila melanogaster."
  103. (2011). Neuronal filtering of multiplexed odour representations."
  104. (2006). Non-topographical contrast enhancement in the olfactory bulb."
  105. (2012). Normalization as a canonical neural computation."
  106. (2002). Odor-stimulated glutamatergic neurotransmission in the zebrafish olfactory bulb."
  107. (2012). Odorant tuning of olfactory crypt cells from juvenile and adult rainbow trout."
  108. (1997). Olfaction in zebrafish: what does a tiny teleost tell us?"
  109. (1994). Olfactory glomeruli in the zebrafish olfactory system form an invariant pattern and are identifiable across animals."
  110. (2002). Olfactory network dynamics and the coding of multidimensional signals."
  111. (2010). Olfactory pattern classification by discrete neuronal network states."
  112. (2014). Olfactory projectome in the zebrafish forebrain revealed by genetic single-neuron labelling."
  113. (2008). Ome sweet ome: what can the genome tell us about the connectome?"
  114. (2010). One rule to grow them all: a general theory of neuronal branching and its practical application."
  115. (1996). Ontogeny of odorant receptor gene expression in zebrafish, Danio rerio."
  116. (2012). Optimization of a GCaMP calcium indicator for neural activity imaging."
  117. (2013). Optogenetics in a transparent animal: circuit function in the larval zebrafish."
  118. (2012). Optogenetics: a new enlightenment age for zebrafish neurobiology."
  119. (1998). Pathfinding of olfactory neuron axons to stereotyped glomerular targets revealed by dynamic imaging in living zebrafish embryos."
  120. (2007). Pattern separation in the dentate gyrus and CA3 of the hippocampus."
  121. (2008). Pharmacological analysis of ionotropic glutamate receptor function in neuronal circuits of the zebrafish olfactory bulb."
  122. (1997). Photon upmanship: why multiphoton imaging is more than a gimmick."
  123. (2014). Phylogenic studies on the olfactory system in vertebrates."
  124. (1990). Postnatal construction of neural circuitry in the mouse olfactory bulb."
  125. (2009). Precision and diversity in an odor map on the olfactory bulb."
  126. (2004). Processing of odor mixtures in the zebrafish olfactory bulb."
  127. (1981). Production of clones of homozygous diploid zebra fish (Brachydanio rerio)."
  128. (2004). Radiation damage in the TEM and SEM."
  129. (2008). Rat olfactory bulb mitral cells receive sparse glomerular inputs."
  130. (2009). Reading the book of memory: sparse sampling versus dense mapping of connectomes."
  131. (1962). Receptive fields, binocular interaction and functional architecture in the cat's visual cortex."
  132. (2006). Reconstruction of firing rate changes across neuronal populations by temporally deconvolved Ca2+ imaging."
  133. (2008). Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy."
  134. (1995). Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the olfactory bulb."
  135. (2003). ScanImage: flexible software for operating laser scanning microscopes."
  136. (2015). SegEM: Efficient Image Analysis for HighResolution Connectomics."
  137. (1989). Self-organization and associative memory: 3rd edition,
  138. (2010). Semi-automated reconstruction of neural circuits using electron microscopy."
  139. (2004). Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure."
  140. (2008). Serial section scanning electron microscopy of adult brain tissue using focused ion beam milling."
  141. (2014). Seung and EyeWirers
  142. (2016). Simultaneous Multi-plane Imaging of Neural Circuits."
  143. (2012). Staining and embedding the whole mouse brain for electron microscopy."
  144. (2012). Structural neurobiology: missing link to a mechanistic understanding of neural computation."
  145. (2011). Structural properties of the Caenorhabditis elegans neuronal network."
  146. (2007). Supervised learning of image restoration with convolutional networks."
  147. (1993). Synaptic circuitry of the retina and olfactory bulb."
  148. (1990). Synaptic organization, local neuronal circuitry, and functional segregation of the teleost olfactory bulb."
  149. (2009). The alarm reaction in fishes--odorants, modulations of responses, neural pathways."
  150. (2011). The big and the small: challenges of imaging the brain's circuits."
  151. (2009). The cellular architecture of the larval zebrafish tectum, as revealed by gal4 enhancer trap lines."
  152. (1975). The elimination of charging artefacts in the scanning electron microscope."
  153. (2000). The molecular architecture of odor and pheromone sensing in mammals."
  154. (1995). The molecular logic of smell."
  155. (1971). The neuron types of the glomerular layer of the olfactory bulb."
  156. (1971). The neuropil of the glomeruli of the olfactory bulb."
  157. (1979). The postnatal development of the main olfactory bulb of the rat."
  158. (1986). The structure of the nervous system of the nematode Caenorhabditis elegans."
  159. (2000). The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio).
  160. (1996). The zebrafish brain: a neuroanatomical comparison with the goldfish." Anat Embryol (Berl)
  161. (2008). Theory and practice of histological techniques, Elsevier Health Sciences.
  162. (2007). Topological reorganization of odor representations in the olfactory bulb."
  163. (2013). Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites."
  164. (2012). TrakEM2 software for neural circuit reconstruction."
  165. (2008). Transparent adult zebrafish as a tool for in vivo transplantation analysis."
  166. (1990). Two-photon laser scanning fluorescence microscopy."
  167. (2015). Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation."
  168. (2006). Uniform serial sectioning for transmission electron microscopy."
  169. (2006). Viral tracing identifies distributed columnar organization in the olfactory bulb."
  170. (2009). visiting scientist in the group of Prof. Richard Hahnloser at the Institute of Neuroinformatics, ETH and
  171. (2011). Visualizing a set of olfactory sensory neurons responding to a bile salt."
  172. (2012). Volume electron microscopy for neuronal circuit reconstruction."
  173. (2008). What is the mammalian dentate gyrus good for?"
  174. (2013). Whole-brain functional imaging at cellular resolution using light-sheet microscopy."
  175. (2001). Whole-cell response characteristics of ciliated and microvillous olfactory receptor neurons to amino acids, pheromone candidates and urine in rainbow trout."
  176. (2013). Why not connectomics?"
  177. (2011). Wiring specificity in the direction-selectivity circuit of the retina."

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