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.
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.
|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|
|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|
|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|
|Zador, Anthony M; Dubnau, Joshua; Oyibo, Hassana K et al. (2012) Sequencing the connectome. PLoS Biol 10:e1001411|