Identification of adult spinal Shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological properties
Spinal cord neurons integrate sensory and descending information to produce motor output. The expression of transcription factors has been used to dissect out the neuronal components of circuits underlying behaviors. However, most of the canonical populations of interneurons are heterogeneous and re...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Neural Circuits |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncir.2022.957084/full |
| _version_ | 1818507601577508864 |
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| author | D. Leonardo Garcia-Ramirez Shayna Singh Jenna R. McGrath Ngoc T. Ha Kimberly J. Dougherty |
| author_facet | D. Leonardo Garcia-Ramirez Shayna Singh Jenna R. McGrath Ngoc T. Ha Kimberly J. Dougherty |
| author_sort | D. Leonardo Garcia-Ramirez |
| collection | DOAJ |
| description | Spinal cord neurons integrate sensory and descending information to produce motor output. The expression of transcription factors has been used to dissect out the neuronal components of circuits underlying behaviors. However, most of the canonical populations of interneurons are heterogeneous and require additional criteria to determine functional subpopulations. Neurons expressing the transcription factor Shox2 can be subclassified based on the co-expression of the transcription factor Chx10 and each subpopulation is proposed to have a distinct connectivity and different role in locomotion. Adult Shox2 neurons have recently been shown to be diverse based on their firing properties. Here, in order to subclassify adult mouse Shox2 neurons, we performed multiple analyses of data collected from whole-cell patch clamp recordings of visually-identified Shox2 neurons from lumbar spinal slices. A smaller set of Chx10 neurons was included in the analyses for validation. We performed k-means and hierarchical unbiased clustering approaches, considering electrophysiological variables. Unlike the categorizations by firing type, the clusters displayed electrophysiological properties that could differentiate between clusters of Shox2 neurons. The presence of clusters consisting exclusively of Shox2 neurons in both clustering techniques suggests that it is possible to distinguish Shox2+Chx10− neurons from Shox2+Chx10+ neurons by electrophysiological properties alone. Computational clusters were further validated by immunohistochemistry with accuracy in a small subset of neurons. Thus, unbiased cluster analysis using electrophysiological properties is a tool that can enhance current interneuronal subclassifications and can complement groupings based on transcription factor and molecular expression. |
| first_indexed | 2024-12-10T22:20:30Z |
| format | Article |
| id | doaj.art-bb354c995e034efcaa8556f83b5b97eb |
| institution | Directory Open Access Journal |
| issn | 1662-5110 |
| language | English |
| last_indexed | 2024-12-10T22:20:30Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neural Circuits |
| spelling | doaj.art-bb354c995e034efcaa8556f83b5b97eb2022-12-22T01:31:19ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102022-08-011610.3389/fncir.2022.957084957084Identification of adult spinal Shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological propertiesD. Leonardo Garcia-RamirezShayna SinghJenna R. McGrathNgoc T. HaKimberly J. DoughertySpinal cord neurons integrate sensory and descending information to produce motor output. The expression of transcription factors has been used to dissect out the neuronal components of circuits underlying behaviors. However, most of the canonical populations of interneurons are heterogeneous and require additional criteria to determine functional subpopulations. Neurons expressing the transcription factor Shox2 can be subclassified based on the co-expression of the transcription factor Chx10 and each subpopulation is proposed to have a distinct connectivity and different role in locomotion. Adult Shox2 neurons have recently been shown to be diverse based on their firing properties. Here, in order to subclassify adult mouse Shox2 neurons, we performed multiple analyses of data collected from whole-cell patch clamp recordings of visually-identified Shox2 neurons from lumbar spinal slices. A smaller set of Chx10 neurons was included in the analyses for validation. We performed k-means and hierarchical unbiased clustering approaches, considering electrophysiological variables. Unlike the categorizations by firing type, the clusters displayed electrophysiological properties that could differentiate between clusters of Shox2 neurons. The presence of clusters consisting exclusively of Shox2 neurons in both clustering techniques suggests that it is possible to distinguish Shox2+Chx10− neurons from Shox2+Chx10+ neurons by electrophysiological properties alone. Computational clusters were further validated by immunohistochemistry with accuracy in a small subset of neurons. Thus, unbiased cluster analysis using electrophysiological properties is a tool that can enhance current interneuronal subclassifications and can complement groupings based on transcription factor and molecular expression.https://www.frontiersin.org/articles/10.3389/fncir.2022.957084/fullspinal cordinterneuronlocomotioncluster analysiselectrophysiology |
| spellingShingle | D. Leonardo Garcia-Ramirez Shayna Singh Jenna R. McGrath Ngoc T. Ha Kimberly J. Dougherty Identification of adult spinal Shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological properties Frontiers in Neural Circuits spinal cord interneuron locomotion cluster analysis electrophysiology |
| title | Identification of adult spinal Shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological properties |
| title_full | Identification of adult spinal Shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological properties |
| title_fullStr | Identification of adult spinal Shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological properties |
| title_full_unstemmed | Identification of adult spinal Shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological properties |
| title_short | Identification of adult spinal Shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological properties |
| title_sort | identification of adult spinal shox2 neuronal subpopulations based on unbiased computational clustering of electrophysiological properties |
| topic | spinal cord interneuron locomotion cluster analysis electrophysiology |
| url | https://www.frontiersin.org/articles/10.3389/fncir.2022.957084/full |
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