Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity
Spinal cord interneurons play critical roles shaping motor output, but their precise identity and connectivity remain unclear. Focusing on the V1 interneuron cardinal class we defined four major V1 subsets in the mouse according to neurogenesis, genetic lineage-tracing, synaptic output to motoneuron...
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eLife Sciences Publications Ltd
2024-11-01
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| Online Access: | https://elifesciences.org/articles/95172 |
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| author | Andrew E Worthy Joanna T Anderson Alicia R Lane Laura J Gomez-Perez Anthony A Wang Ronald W Griffith Andre F Rivard Jay B Bikoff Francisco J Alvarez |
| author_facet | Andrew E Worthy Joanna T Anderson Alicia R Lane Laura J Gomez-Perez Anthony A Wang Ronald W Griffith Andre F Rivard Jay B Bikoff Francisco J Alvarez |
| author_sort | Andrew E Worthy |
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| description | Spinal cord interneurons play critical roles shaping motor output, but their precise identity and connectivity remain unclear. Focusing on the V1 interneuron cardinal class we defined four major V1 subsets in the mouse according to neurogenesis, genetic lineage-tracing, synaptic output to motoneurons, and synaptic inputs from muscle afferents. Sequential neurogenesis delineates different V1 subsets: two early born (Renshaw and Pou6f2) and two late born (Foxp2 and Sp8). Early born Renshaw cells and late born Foxp2-V1 interneurons are tightly coupled to motoneurons, while early born Pou6f2-V1 and late born Sp8-V1 interneurons are not, indicating that timing of neurogenesis does not correlate with motoneuron targeting. V1 clades also differ in cell numbers and diversity. Lineage labeling shows that the Foxp2-V1 clade contains over half of all V1 interneurons, provides the largest inhibitory input to motoneuron cell bodies, and includes subgroups that differ in birthdate, location, and proprioceptive input. Notably, one Foxp2-V1 subgroup, defined by postnatal Otp expression, is positioned near the LMC and receives substantial input from proprioceptors, consistent with an involvement in reciprocal inhibitory pathways. Combined tracing of ankle flexor sensory afferents and interneurons monosynaptically connected to ankle extensors confirmed placement of Foxp2-V1 interneurons in reciprocal inhibitory pathways. Our results validate previously proposed V1 clades as unique functional subtypes that differ in circuit placement, with Foxp2-V1 cells forming the most heterogeneous subgroup. We discuss how V1 organizational diversity enables understanding of their roles in motor control, with implications for their diverse ontogenetic and phylogenetic origins. |
| format | Article |
| id | doaj-art-76542f0fc4a345f1a807feae5c19dfd8 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-76542f0fc4a345f1a807feae5c19dfd82025-08-20T01:52:49ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011310.7554/eLife.95172Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneityAndrew E Worthy0https://orcid.org/0000-0002-9992-2675Joanna T Anderson1Alicia R Lane2https://orcid.org/0000-0002-6404-7559Laura J Gomez-Perez3Anthony A Wang4Ronald W Griffith5Andre F Rivard6Jay B Bikoff7Francisco J Alvarez8https://orcid.org/0000-0001-7011-3244Department of Physiology, Emory University School of Medicine, Atlanta, United States; Department of Cell Biology, Emory University School of Medicine, Atlanta, United StatesDepartment of Cell Biology, Emory University School of Medicine, Atlanta, United StatesDepartment of Cell Biology, Emory University School of Medicine, Atlanta, United StatesDepartment of Cell Biology, Emory University School of Medicine, Atlanta, United StatesDepartment of Physiology, Emory University School of Medicine, Atlanta, United StatesDepartment of Physiology, Emory University School of Medicine, Atlanta, United States; Department of Cell Biology, Emory University School of Medicine, Atlanta, United StatesDepartment of Cell Biology, Emory University School of Medicine, Atlanta, United StatesDepartment of Developmental Neurobiology, St Jude Children’s Research Hospital, Memphis, United StatesDepartment of Physiology, Emory University School of Medicine, Atlanta, United States; Department of Cell Biology, Emory University School of Medicine, Atlanta, United StatesSpinal cord interneurons play critical roles shaping motor output, but their precise identity and connectivity remain unclear. Focusing on the V1 interneuron cardinal class we defined four major V1 subsets in the mouse according to neurogenesis, genetic lineage-tracing, synaptic output to motoneurons, and synaptic inputs from muscle afferents. Sequential neurogenesis delineates different V1 subsets: two early born (Renshaw and Pou6f2) and two late born (Foxp2 and Sp8). Early born Renshaw cells and late born Foxp2-V1 interneurons are tightly coupled to motoneurons, while early born Pou6f2-V1 and late born Sp8-V1 interneurons are not, indicating that timing of neurogenesis does not correlate with motoneuron targeting. V1 clades also differ in cell numbers and diversity. Lineage labeling shows that the Foxp2-V1 clade contains over half of all V1 interneurons, provides the largest inhibitory input to motoneuron cell bodies, and includes subgroups that differ in birthdate, location, and proprioceptive input. Notably, one Foxp2-V1 subgroup, defined by postnatal Otp expression, is positioned near the LMC and receives substantial input from proprioceptors, consistent with an involvement in reciprocal inhibitory pathways. Combined tracing of ankle flexor sensory afferents and interneurons monosynaptically connected to ankle extensors confirmed placement of Foxp2-V1 interneurons in reciprocal inhibitory pathways. Our results validate previously proposed V1 clades as unique functional subtypes that differ in circuit placement, with Foxp2-V1 cells forming the most heterogeneous subgroup. We discuss how V1 organizational diversity enables understanding of their roles in motor control, with implications for their diverse ontogenetic and phylogenetic origins.https://elifesciences.org/articles/95172spinal cordmotorFoxp2limb controlreciprocal inhibitionRenshaw cell |
| spellingShingle | Andrew E Worthy Joanna T Anderson Alicia R Lane Laura J Gomez-Perez Anthony A Wang Ronald W Griffith Andre F Rivard Jay B Bikoff Francisco J Alvarez Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity eLife spinal cord motor Foxp2 limb control reciprocal inhibition Renshaw cell |
| title | Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity |
| title_full | Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity |
| title_fullStr | Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity |
| title_full_unstemmed | Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity |
| title_short | Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity |
| title_sort | spinal v1 inhibitory interneuron clades differ in birthdate projections to motoneurons and heterogeneity |
| topic | spinal cord motor Foxp2 limb control reciprocal inhibition Renshaw cell |
| url | https://elifesciences.org/articles/95172 |
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