Genome-Wide Analysis of Differential Gene Expression and Splicing in Excitatory Neurons and Interneuron Subtypes
Name
958.full.pdf
Description
Published version
Size
3.52 MB
Format
Unknown
Checksum (MD5)
69318e442e8dc3a6225e4968a5a155b9
Author(s)
Huntley, Melanie A.
Srinivasan, Karpagam
Friedman, Brad A.
Wang, Tzu-Ming
Yee, Ada X.
Wang, Yuanyuan
Kaminker, Josh S.
Sheng, Morgan
Hansen, David V.
Hanson, Jesse E.
Date Issued
December 2019
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Version
Final published version
Abstract
Cortical circuit activity is shaped by the parvalbumin (PV) and somatostatin (SST) interneurons that inhibit principal excitatory (EXC) neurons and the vasoactive intestinal peptide (VIP) interneurons that suppress activation of other interneurons. To understand the molecular-genetic basis of functional specialization and identify potential drug targets specific to each neuron subtype, we performed a genome wide assessment of both gene expression and splicing across EXC, PV, SST and VIP neurons from male and female mouse brains. These results reveal numerous examples where neuron subtype-specific gene expression, as well as splice-isoform usage, can explain functional differences between neuron subtypes, including in presynaptic plasticity, postsynaptic receptor function, and synaptic connectivity specification. We provide a searchable web resource for exploring differential mRNA expression and splice form usage between excitatory, PV, SST, and VIP neurons (http://research-pub.gene.com/NeuronSubtypeTranscriptomes). This resource, combining a unique new dataset and novel application of analysis methods to multiple relevant datasets, identifies numerous potential drug targets for manipulating circuit function, reveals neuron subtype-specific roles for disease-linked genes, and is useful for understanding gene expression changes observed in human patient brains.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1523/jneurosci.1615-19.2019
