Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons
Expressions of voltage-gated sodium channels Nav1.1 and Nav1.2, encoded by SCN1A and SCN2A genes, respectively, have been reported to be mutually exclusive in most brain regions. In juvenile and adult neocortex, Nav1.1 is predominantly expressed in inhibitory neurons while Nav1.2 is in excitatory ne...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/87495 |
| _version_ | 1797821771026530304 |
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| author | Tetsushi Yamagata Ikuo Ogiwara Tetsuya Tatsukawa Toshimitsu Suzuki Yuka Otsuka Nao Imaeda Emi Mazaki Ikuyo Inoue Natsuko Tokonami Yurina Hibi Shigeyoshi Itohara Kazuhiro Yamakawa |
| author_facet | Tetsushi Yamagata Ikuo Ogiwara Tetsuya Tatsukawa Toshimitsu Suzuki Yuka Otsuka Nao Imaeda Emi Mazaki Ikuyo Inoue Natsuko Tokonami Yurina Hibi Shigeyoshi Itohara Kazuhiro Yamakawa |
| author_sort | Tetsushi Yamagata |
| collection | DOAJ |
| description | Expressions of voltage-gated sodium channels Nav1.1 and Nav1.2, encoded by SCN1A and SCN2A genes, respectively, have been reported to be mutually exclusive in most brain regions. In juvenile and adult neocortex, Nav1.1 is predominantly expressed in inhibitory neurons while Nav1.2 is in excitatory neurons. Although a distinct subpopulation of layer V (L5) neocortical excitatory neurons were also reported to express Nav1.1, their nature has been uncharacterized. In hippocampus, Nav1.1 has been proposed to be expressed only in inhibitory neurons. By using newly generated transgenic mouse lines expressing Scn1a promoter-driven green fluorescent protein (GFP), here we confirm the mutually exclusive expressions of Nav1.1 and Nav1.2 and the absence of Nav1.1 in hippocampal excitatory neurons. We also show that Nav1.1 is expressed in inhibitory and a subpopulation of excitatory neurons not only in L5 but all layers of neocortex. By using neocortical excitatory projection neuron markers including FEZF2 for L5 pyramidal tract (PT) and TBR1 for layer VI (L6) cortico-thalamic (CT) projection neurons, we further show that most L5 PT neurons and a minor subpopulation of layer II/III (L2/3) cortico-cortical (CC) neurons express Nav1.1 while the majority of L6 CT, L5/6 cortico-striatal (CS), and L2/3 CC neurons express Nav1.2. These observations now contribute to the elucidation of pathological neural circuits for diseases such as epilepsies and neurodevelopmental disorders caused by SCN1A and SCN2A mutations. |
| first_indexed | 2024-03-13T09:57:42Z |
| format | Article |
| id | doaj.art-7469f0ad906948b3991e9403aaccb070 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T09:57:42Z |
| publishDate | 2023-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7469f0ad906948b3991e9403aaccb0702023-05-23T12:06:03ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.87495Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neuronsTetsushi Yamagata0Ikuo Ogiwara1https://orcid.org/0000-0003-4826-1456Tetsuya Tatsukawa2Toshimitsu Suzuki3Yuka Otsuka4Nao Imaeda5Emi Mazaki6Ikuyo Inoue7Natsuko Tokonami8Yurina Hibi9Shigeyoshi Itohara10Kazuhiro Yamakawa11https://orcid.org/0000-0002-1478-4390Department of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Laboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, JapanLaboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, Japan; Department of Physiology, Nippon Medical School, Tokyo, JapanLaboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, JapanDepartment of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Laboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, JapanDepartment of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanDepartment of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanLaboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, JapanLaboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, JapanLaboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, JapanDepartment of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanLaboratory for Behavioral Genetics, RIKEN Center for Brain Science, Wako, JapanDepartment of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Laboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, JapanExpressions of voltage-gated sodium channels Nav1.1 and Nav1.2, encoded by SCN1A and SCN2A genes, respectively, have been reported to be mutually exclusive in most brain regions. In juvenile and adult neocortex, Nav1.1 is predominantly expressed in inhibitory neurons while Nav1.2 is in excitatory neurons. Although a distinct subpopulation of layer V (L5) neocortical excitatory neurons were also reported to express Nav1.1, their nature has been uncharacterized. In hippocampus, Nav1.1 has been proposed to be expressed only in inhibitory neurons. By using newly generated transgenic mouse lines expressing Scn1a promoter-driven green fluorescent protein (GFP), here we confirm the mutually exclusive expressions of Nav1.1 and Nav1.2 and the absence of Nav1.1 in hippocampal excitatory neurons. We also show that Nav1.1 is expressed in inhibitory and a subpopulation of excitatory neurons not only in L5 but all layers of neocortex. By using neocortical excitatory projection neuron markers including FEZF2 for L5 pyramidal tract (PT) and TBR1 for layer VI (L6) cortico-thalamic (CT) projection neurons, we further show that most L5 PT neurons and a minor subpopulation of layer II/III (L2/3) cortico-cortical (CC) neurons express Nav1.1 while the majority of L6 CT, L5/6 cortico-striatal (CS), and L2/3 CC neurons express Nav1.2. These observations now contribute to the elucidation of pathological neural circuits for diseases such as epilepsies and neurodevelopmental disorders caused by SCN1A and SCN2A mutations.https://elifesciences.org/articles/87495SCN1ASCN2Apyramidal tractFEZF2TBR1 |
| spellingShingle | Tetsushi Yamagata Ikuo Ogiwara Tetsuya Tatsukawa Toshimitsu Suzuki Yuka Otsuka Nao Imaeda Emi Mazaki Ikuyo Inoue Natsuko Tokonami Yurina Hibi Shigeyoshi Itohara Kazuhiro Yamakawa Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons eLife SCN1A SCN2A pyramidal tract FEZF2 TBR1 |
| title | Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons |
| title_full | Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons |
| title_fullStr | Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons |
| title_full_unstemmed | Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons |
| title_short | Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons |
| title_sort | scn1a gfp transgenic mouse revealed nav1 1 expression in neocortical pyramidal tract projection neurons |
| topic | SCN1A SCN2A pyramidal tract FEZF2 TBR1 |
| url | https://elifesciences.org/articles/87495 |
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