Neural circuits are composed of networks of specific cell types that are interconnected in precise patterns to give rise to normal brain function. Past studies have investigated the rates of connections that are formed by cultured neurons in vitro and these have revealed abnormalities both in a mouse model of autism (MeCP2 KO mice) and for human induced pluripotent stem cell (hiPSC)-derived neurons from schizophrenic patients (Brennand et al., 2011). But simple separation of cortical neurons into just excitatory versus inhibitory groups barely scratches the surface of the diversity of cortical cell types, the known specificity of connections between specific cell types in the abnormal or normal brain. In Project 5 we propose to develop and then implement novel tools that will allow assays of the cell-type specificity of connections that are formed in cultures of hiPSC- derived neurons. These assays are based on the use of glycoprotein deleted rabies viruses for trans-synaptic labeling of connected neurons, and conditional expression of EnvA/TVA targeting systems for directing the initial infection of rabies virus to specific cell types (Wickersham et al., 2007b; Marshel et al., 2010; Wall et al., 2010)

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California, San Diego
La Jolla
United States
Zip Code
Mesci, Pinar; Macia, Angela; LaRock, Christopher N et al. (2018) Modeling neuro-immune interactions during Zika virus infection. Hum Mol Genet 27:41-52
Chailangkarn, Thanathom; Noree, Chalongrat; Muotri, Alysson R (2018) The contribution of GTF2I haploinsufficiency to Williams syndrome. Mol Cell Probes 40:45-51
Brito, Anita; Russo, Fabiele Baldino; Muotri, Alysson Renato et al. (2018) Autism spectrum disorders and disease modeling using stem cells. Cell Tissue Res 371:153-160
Fernandes, Isabella R; Cruz, Ana C P; Ferrasa, Adriano et al. (2018) Genetic variations on SETD5 underlying autistic conditions. Dev Neurobiol 78:500-518
Mesci, Pinar; Macia, Angela; Moore, Spencer M et al. (2018) Blocking Zika virus vertical transmission. Sci Rep 8:1218
Beltrão-Braga, Patricia C B; Muotri, Alysson R (2017) Modeling autism spectrum disorders with human neurons. Brain Res 1656:49-54
Song, Yan; Botvinnik, Olga B; Lovci, Michael T et al. (2017) Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation. Mol Cell 67:148-161.e5
de Souza, Janaina S; Carromeu, Cassiano; Torres, Laila B et al. (2017) IGF1 neuronal response in the absence of MECP2 is dependent on TRalpha 3. Hum Mol Genet 26:270-281
Shiryaev, Sergey A; Mesci, Pinar; Pinto, Antonella et al. (2017) Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis. Sci Rep 7:15771
Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E et al. (2017) Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA sequencing. Nat Immunol 18:422-432

Showing the most recent 10 out of 17 publications