Corticospinal circuit remodeling after central nervous system injury is dependent on neuronal activity
| Autor: | Florence M. Bareyre, Carmen K. Denecke, Martin Kerschensteiner, Peter M.J. Bradley, Anja Schmalz, Almir Aljovic |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Central Nervous System Mice 129 Strain Immunology Central nervous system Models Neurological Pyramidal Tracts Mice Transgenic Biology Receptors N-Methyl-D-Aspartate 03 medical and health sciences 0302 clinical medicine Postsynaptic potential medicine Immunology and Allergy Premovement neuronal activity Animals Axon Cyclic AMP Response Element-Binding Protein Spinal cord injury Spinal Cord Injuries Research Articles Mice Knockout Neurons Brief Definitive Report Recovery of Function medicine.disease Axons Nerve Regeneration Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system Corticospinal tract NMDA receptor Female Neuron Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 |
| Popis: | This study investigates the principles of target selection during the remodeling of neuronal circuits following spinal cord injury. It demonstrates that remodeling axons select their postsynaptic partners in an activity-dependent competitive process that is critical for functional recovery after injury. The remodeling of supraspinal axonal circuits mediates functional recovery after spinal cord injury. This process critically depends on the selection of appropriate synaptic connections between cortical projection and spinal relay neurons. To unravel the principles that guide this target selection, we used genetic and chemogenetic tools to modulate NMDA receptor (NMDAR) integrity and function, CREB-mediated transcription, and neuronal firing of relay neurons during injury-induced corticospinal remodeling. We show that NMDAR signaling and CREB-mediated transcription maintain nascent corticospinal tract (CST)–relay neuron contacts. These activity-dependent signals act during a defined period of circuit remodeling and do not affect mature or uninjured circuits. Furthermore, chemogenetic modulation of relay neuron activity reveals that the regrowing CST axons select their postsynaptic partners in a competitive manner and that preventing such activity-dependent shaping of corticospinal circuits limits motor recovery after spinal cord injury. Graphical Abstract |
| Databáze: | OpenAIRE |
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