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PLoS One. 2014 Mar 14;9(3):e91744. doi: 10.1371/journal.pone.0091744. eCollection 2014.

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

Author information

1
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
2
Imaging Platform at the Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
3
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
4
RNAi Platform, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.

Abstract

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.

PMID:
24633176
PMCID:
PMC3954765
DOI:
10.1371/journal.pone.0091744
[Indexed for MEDLINE]
Free PMC Article
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