Abstract

The brain is an extremely complex network, consisting of billions of neurons connected by trillions of synapses. The details of these connections-which neurons form synaptic connections with which other neurons-are crucial in determining brain function. Malformation of these connections during prenatal and early postnatal development can lead to mental retardation, autism or schizophrenia;loss of specific connections later in life is associated with neurodegenerative diseases such as Alzheimer's. An efficient method for determining the brain's wiring diagram would transform neuroscience research. We propose to develop a method for exploiting high-throughput DNA sequencing to probe the connectivity of neural circuits at single-neuron resolution.

Public Health Relevance

Many neuropsychiatric and neurodegenerative diseases, including autism, schizophrenia, mental retardation and Alzheimer's disease, result in the loss of specific connections in the brain. We propose to develop a method for identifying these connections in animal models of disease. Our method will have a profound impact on understanding the causes of these diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS073129-03
Application #
8268465
Study Section
Special Emphasis Panel (ZRG1-BCMB-A (51))
Program Officer
Gwinn, Katrina
Project Start
2010-09-27
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$464,475
Indirect Cost
$216,975

  Institution

Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724

  Publications

Han, Yunyun; Kebschull, Justus M; Campbell, Robert A A et al. (2018) The logic of single-cell projections from visual cortex. Nature 556:51-56
Kebschull, Justus M; Garcia da Silva, Pedro; Reid, Ashlan P et al. (2016) High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA. Neuron 91:975-987
Kebschull, Justus M; Garcia da Silva, Pedro; Zador, Anthony M (2016) A New Defective Helper RNA to Produce Recombinant Sindbis Virus that Infects Neurons but does not Propagate. Front Neuroanat 10:56
Kebschull, Justus M; Zador, Anthony M (2015) Sources of PCR-induced distortions in high-throughput sequencing data sets. Nucleic Acids Res 43:e143
Oyibo, Hassana K; Znamenskiy, Petr; Oviedo, Hysell V et al. (2014) Long-term Cre-mediated retrograde tagging of neurons using a novel recombinant pseudorabies virus. Front Neuroanat 8:86
Peikon, Ian D; Gizatullina, Diana I; Zador, Anthony M (2014) In vivo generation of DNA sequence diversity for cellular barcoding. Nucleic Acids Res 42:e127
Zador, Anthony M; Dubnau, Joshua; Oyibo, Hassana K et al. (2012) Sequencing the connectome. PLoS Biol 10:e1001411