Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice
Intratelencephalic neurons are a crucial class of cortical principal neurons that heavily innervate the striatum and cortical areas bilaterally. Their extensive cortico-cortical and cortico-striatal connectivity enables sensorimotor integration within the telencephalon, but their role in motor contr...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003577 |
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| author | Mihai Atudorei Christian del Agua Villa Ulrik Gether Maria Angela Cenci Hartwig Roman Siebner Mattias Rickhag |
| author_facet | Mihai Atudorei Christian del Agua Villa Ulrik Gether Maria Angela Cenci Hartwig Roman Siebner Mattias Rickhag |
| author_sort | Mihai Atudorei |
| collection | DOAJ |
| description | Intratelencephalic neurons are a crucial class of cortical principal neurons that heavily innervate the striatum and cortical areas bilaterally. Their extensive cortico-cortical and cortico-striatal connectivity enables sensorimotor integration within the telencephalon, but their role in motor control remains poorly understood. Here, we used a chemogenetic approach to explore the role of intratelencephalic neurons in spontaneous locomotor activity. Bilateral chemogenetic activation of intratelencephalic Tlx3+ neurons in the mouse motor cortex reduced spontaneous locomotor activity in the open field, increasing states of freezing and immobility. This anti-motor effect was achieved in separate experiments with either administration of two chemogenetic actuators, clozapine N-oxide and deschloroclozapine. A systemic administration of the dopamine D1 receptor agonist SKF82958 reversed the chemogenetic effect on locomotor activity. Selective chemogenetic stimulation of intratelencephalic neurons was confirmed through post-mortem c-Fos quantification in cortical layer 5 Tlx3+ neurons. The results establish a causal link between the activity level of intratelencephalic neurons in the motor cortex, spontaneous locomotor activity in the open field, and the dopamine system. The findings are compatible with the hypothesis that intratelencephalic neurons regulate spontaneous motor behavior via its bilateral cortico-striatal projections. |
| format | Article |
| id | doaj-art-4a178c16f1454c7bafead03969e9ad4f |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-4a178c16f1454c7bafead03969e9ad4f2025-01-07T04:17:05ZengElsevierNeurobiology of Disease1095-953X2025-01-01204106755Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in miceMihai Atudorei0Christian del Agua Villa1Ulrik Gether2Maria Angela Cenci3Hartwig Roman Siebner4Mattias Rickhag5Danish Research Centre for Magnetic Resonance (DRCMR), Department of Radiology and Nuclear Medicine, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, DenmarkDanish Research Centre for Magnetic Resonance (DRCMR), Department of Radiology and Nuclear Medicine, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, DenmarkDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Experimental Medical Science, Lund University, SwedenDanish Research Centre for Magnetic Resonance (DRCMR), Department of Radiology and Nuclear Medicine, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Neurology, Copenhagen University Hospital - Bispebjerg, Copenhagen, Denmark; Corresponding authors at: Danish Research Centre for Magnetic Resonance (DRCMR), Department of Radiology and Nuclear Medicine, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.Danish Research Centre for Magnetic Resonance (DRCMR), Department of Radiology and Nuclear Medicine, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Corresponding authors at: Danish Research Centre for Magnetic Resonance (DRCMR), Department of Radiology and Nuclear Medicine, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.Intratelencephalic neurons are a crucial class of cortical principal neurons that heavily innervate the striatum and cortical areas bilaterally. Their extensive cortico-cortical and cortico-striatal connectivity enables sensorimotor integration within the telencephalon, but their role in motor control remains poorly understood. Here, we used a chemogenetic approach to explore the role of intratelencephalic neurons in spontaneous locomotor activity. Bilateral chemogenetic activation of intratelencephalic Tlx3+ neurons in the mouse motor cortex reduced spontaneous locomotor activity in the open field, increasing states of freezing and immobility. This anti-motor effect was achieved in separate experiments with either administration of two chemogenetic actuators, clozapine N-oxide and deschloroclozapine. A systemic administration of the dopamine D1 receptor agonist SKF82958 reversed the chemogenetic effect on locomotor activity. Selective chemogenetic stimulation of intratelencephalic neurons was confirmed through post-mortem c-Fos quantification in cortical layer 5 Tlx3+ neurons. The results establish a causal link between the activity level of intratelencephalic neurons in the motor cortex, spontaneous locomotor activity in the open field, and the dopamine system. The findings are compatible with the hypothesis that intratelencephalic neurons regulate spontaneous motor behavior via its bilateral cortico-striatal projections.http://www.sciencedirect.com/science/article/pii/S0969996124003577Cortico-striatal projectionsChemogeneticsLocomotor activityIntratelencephalic neuronsCortical microcircuit |
| spellingShingle | Mihai Atudorei Christian del Agua Villa Ulrik Gether Maria Angela Cenci Hartwig Roman Siebner Mattias Rickhag Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice Neurobiology of Disease Cortico-striatal projections Chemogenetics Locomotor activity Intratelencephalic neurons Cortical microcircuit |
| title | Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice |
| title_full | Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice |
| title_fullStr | Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice |
| title_full_unstemmed | Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice |
| title_short | Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice |
| title_sort | bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice |
| topic | Cortico-striatal projections Chemogenetics Locomotor activity Intratelencephalic neurons Cortical microcircuit |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003577 |
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