Genome-wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes
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 functi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Society for Neuroscience
2021
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| Online Access: | https://hdl.handle.net/1721.1/135300 |
| _version_ | 1811090268199321600 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Huntley, Melanie A |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:40:22Z |
| format | Article |
| id | mit-1721.1/135300 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:40:22Z |
| publishDate | 2021 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/1353002021-10-28T03:34:39Z Genome-wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes 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 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. 2021-10-27T20:22:52Z 2021-10-27T20:22:52Z 2020 2021-03-24T17:18:32Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135300 en 10.1523/JNEUROSCI.1615-19.2019 Journal of Neuroscience Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Society for Neuroscience Journal of Neuroscience |
| spellingShingle | 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 Genome-wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes |
| title | Genome-wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes |
| title_full | Genome-wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes |
| title_fullStr | Genome-wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes |
| title_full_unstemmed | Genome-wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes |
| title_short | Genome-wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes |
| title_sort | genome wide analysis of differential gene expression and splicing in excitatory neurons and interneuron subtypes |
| url | https://hdl.handle.net/1721.1/135300 |
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