Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons
Neocortical GABAergic interneuron migration and thalamo-cortical axon (TCA) pathfinding follow similar trajectories and timing, suggesting they may be interdependent. The mechanisms that regulate the radial dispersion of neocortical interneurons are incompletely understood. Here we report that disru...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-12-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/20770 |
| _version_ | 1811202573057654784 |
|---|---|
| author | Sabrina Zechel Yasushi Nakagawa Carlos F Ibáñez |
| author_facet | Sabrina Zechel Yasushi Nakagawa Carlos F Ibáñez |
| author_sort | Sabrina Zechel |
| collection | DOAJ |
| description | Neocortical GABAergic interneuron migration and thalamo-cortical axon (TCA) pathfinding follow similar trajectories and timing, suggesting they may be interdependent. The mechanisms that regulate the radial dispersion of neocortical interneurons are incompletely understood. Here we report that disruption of TCA innervation, or TCA-derived glutamate, affected the laminar distribution of GABAergic interneurons in mouse neocortex, resulting in abnormal accumulation in deep layers of interneurons that failed to switch from tangential to radial orientation. Expression of the KCC2 cotransporter was elevated in interneurons of denervated cortex, and KCC2 deletion restored normal interneuron lamination in the absence of TCAs. Disruption of interneuron NMDA receptors or pharmacological inhibition of calpain also led to increased KCC2 expression and defective radial dispersion of interneurons. Thus, although TCAs are not required to guide the tangential migration of GABAergic interneurons, they provide crucial signals that restrict interneuron KCC2 levels, allowing coordinated neocortical invasion of TCAs and interneurons. |
| first_indexed | 2024-04-12T02:40:55Z |
| format | Article |
| id | doaj.art-8e6fbf5035a34567a6f89f0fc7604fd3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:40:55Z |
| publishDate | 2016-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8e6fbf5035a34567a6f89f0fc7604fd32022-12-22T03:51:18ZengeLife Sciences Publications LtdeLife2050-084X2016-12-01510.7554/eLife.20770Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneuronsSabrina Zechel0Yasushi Nakagawa1Carlos F Ibáñez2Department of Neuroscience, Karolinska Institute, Stockholm, SwedenDepartment of Neuroscience, University of Minnesota Medical School, Minneapolis, United StatesDepartment of Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Physiology, National University of Singapore, Singapore, Singapore; Life Sciences Institute, National University of Singapore, Singapore, SingaporeNeocortical GABAergic interneuron migration and thalamo-cortical axon (TCA) pathfinding follow similar trajectories and timing, suggesting they may be interdependent. The mechanisms that regulate the radial dispersion of neocortical interneurons are incompletely understood. Here we report that disruption of TCA innervation, or TCA-derived glutamate, affected the laminar distribution of GABAergic interneurons in mouse neocortex, resulting in abnormal accumulation in deep layers of interneurons that failed to switch from tangential to radial orientation. Expression of the KCC2 cotransporter was elevated in interneurons of denervated cortex, and KCC2 deletion restored normal interneuron lamination in the absence of TCAs. Disruption of interneuron NMDA receptors or pharmacological inhibition of calpain also led to increased KCC2 expression and defective radial dispersion of interneurons. Thus, although TCAs are not required to guide the tangential migration of GABAergic interneurons, they provide crucial signals that restrict interneuron KCC2 levels, allowing coordinated neocortical invasion of TCAs and interneurons.https://elifesciences.org/articles/20770Gbx2KCC2neocortexcell migrationTCAcalpain |
| spellingShingle | Sabrina Zechel Yasushi Nakagawa Carlos F Ibáñez Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons eLife Gbx2 KCC2 neocortex cell migration TCA calpain |
| title | Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons |
| title_full | Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons |
| title_fullStr | Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons |
| title_full_unstemmed | Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons |
| title_short | Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons |
| title_sort | thalamo cortical axons regulate the radial dispersion of neocortical gabaergic interneurons |
| topic | Gbx2 KCC2 neocortex cell migration TCA calpain |
| url | https://elifesciences.org/articles/20770 |
| work_keys_str_mv | AT sabrinazechel thalamocorticalaxonsregulatetheradialdispersionofneocorticalgabaergicinterneurons AT yasushinakagawa thalamocorticalaxonsregulatetheradialdispersionofneocorticalgabaergicinterneurons AT carlosfibanez thalamocorticalaxonsregulatetheradialdispersionofneocorticalgabaergicinterneurons |