Brains contain large number of neurons whose connections, formed by axonal and dendritic processes, are the structural underpinning of electrical circuits that control behavior. The analysis of circuits is of great importance. All acts of fine motor control, memory formation and cognition can only be understood if the circuitry within the brain compartments dealing with these functions is known. Likewise, the insight into psychiatric disease mechanisms and their pharmacological treatment requires brain circuitry to be known in detail. For example, recent findings suggest that diseases like autism or schizophrenia can be understood in terms of abnormalities in the micro- circuitry of the prefrontal cortex. We propose in this grant to develop and utilize bioinformatics tools that enable us to address circuitry in the Drosophila brain. The Drosophila central brain is formed by a stereotyped set of approximately 100 paired lineages, each one derived from one neuroblast. Neurons of one lineage form processes that spread within discrete compartments of the brain. Lineages thereby represent the most appropriate structural/developmental units of brain macro-circuitry. Reconstructing the projection of all lineages means to have generated an accurate map of Drosophila brain circuitry at the level of neuron populations ("macro-circuitry"). We propose to generate this map, presented in a standardized electronic format that is accessible to the neurobiology community. In addition, we will reconstruct circuitry at the level of individual synapses ("micro-circuitry"), which requires electron microscopy (EM). We have developed the software required for the automated recording, registration and navigation of large EM image data sets. We will further improve and use these tools to generate a digital EM dataset that, for the first time, encompasses the entire brain of an animal with a sizeable number of structurally complex neurons. Our software allows us to efficiently reconstruct the neural networks encountered in different parts of the brain. We anticipate that we will be able to learn structural principles about neural network that have general application.

Public Health Relevance

Drosophila serves as an important model to study how neural circuits develop and function to control behavior. The Drosophila brain is formed by an invariant set of lineages, each of which is derived from a unique neural stem cell (neuroblast) and forms a genetic and structural unit of the brain. We will use bioinformatics tools to generate a comprehensive digital atlas of the Drosophila brain lineages and their connections, which can be used by the neurobiology community at large to map and analyze neurons and circuits.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS054814-07
Application #
8215675
Study Section
Neurotechnology Study Section (NT)
Program Officer
Liu, Yuan
Project Start
2006-02-01
Project End
2015-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
7
Fiscal Year
2012
Total Cost
$330,138
Indirect Cost
$115,763
Name
University of California Los Angeles
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Das, Abhijit; Gupta, Tripti; Davla, Sejal et al. (2013) Neuroblast lineage-specific origin of the neurons of the Drosophila larval olfactory system. Dev Biol 373:322-37
Bailly, Xavier; Reichert, Heinrich; Hartenstein, Volker (2013) The urbilaterian brain revisited: novel insights into old questions from new flatworm clades. Dev Genes Evol 223:149-57
Hartenstein, Volker (2013) Stem cells in the context of evolution and development. Dev Genes Evol 223:1-3
Wong, Darren C; Lovick, Jennifer K; Ngo, Kathy T et al. (2013) Postembryonic lineages of the Drosophila brain: II. Identification of lineage projection patterns based on MARCM clones. Dev Biol 384:258-89
Hartenstein, Volker; Wodarz, Andreas (2013) Initial neurogenesis in Drosophila. Wiley Interdiscip Rev Dev Biol 2:701-21
Gross, Garrett G; Lone, G Mohiddin; Leung, Lok Kwan et al. (2013) X11/Mint genes control polarized localization of axonal membrane proteins in vivo. J Neurosci 33:8575-86
Lovick, Jennifer K; Ngo, Kathy T; Omoto, Jaison J et al. (2013) Postembryonic lineages of the Drosophila brain: I. Development of the lineage-associated fiber tracts. Dev Biol 384:228-57
Takashima, Shigeo; Gold, David; Hartenstein, Volker (2013) Stem cells and lineages of the intestine: a developmental and evolutionary perspective. Dev Genes Evol 223:85-102
Hartenstein, Volker (2011) Morphological diversity and development of glia in Drosophila. Glia 59:1237-52
Sprecher, Simon G; Cardona, Albert; Hartenstein, Volker (2011) The Drosophila larval visual system: high-resolution analysis of a simple visual neuropil. Dev Biol 358:33-43

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