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PLoS One DOI:10.1371/journal.pone.0091744

High content image analysis identifies novel regulators of synaptogenesis in a high-throughput RNAi screen of primary neurons.

Publication TypeJournal Article
Year of Publication2014
AuthorsNieland, TJF, Logan, DJ, Saulnier, J, Lam, D, Johnson, C, Root, DE, Carpenter, AE, Sabatini, BL
JournalPLoS One
Date Published2014
KeywordsAlgorithms, Animals, Automation, Laboratory, Gene Expression Regulation, High-Throughput Screening Assays, Mice, Microscopy, Fluorescence, Neurons, RNA Interference, RNA, Small Interfering, Synapses

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.


Alternate JournalPLoS ONE
PubMed ID24633176
PubMed Central IDPMC3954765
Grant ListR01 GM089652 / GM / NIGMS NIH HHS / United States
MH095096 / MH / NIMH NIH HHS / United States