Spinal Glutamatergic Neurons Defined by EphA4 Signaling Are Essential Components of Normal Locomotor Circuits
| Autor: | Peter Löw, Ole Kiehn, Hiroshi Nishimaru, Yuka Kunugise, Ramon Reig, Lotta Borgius, Shigeyoshi Itohara, Takuji Iwasato, Vanessa Caldeira |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Lameness Animal Pyramidal Tracts Glutamic Acid Motor Activity Biology Efferent Pathways Mice Glutamatergic Interneurons medicine Animals Chimerin 1 Mice Knockout General Neuroscience Receptor EphA4 Central pattern generator Articles Spinal cord Gait medicine.anatomical_structure Spinal Cord nervous system Forebrain Corticospinal tract Central Pattern Generators Excitatory postsynaptic potential Female Signal transduction Neuroscience Locomotion Signal Transduction |
| Zdroj: | The Journal of Neuroscience. 34:3841-3853 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.4992-13.2014 |
| Popis: | EphA4 signaling is essential for the spatiotemporal organization of neuronal circuit formation. In mice, deletion of this signaling pathway causes aberrant midline crossing of axons from both brain and spinal neurons and the complete knock-outs (KOs) exhibit a pronounced change in motor behavior, where alternating gaits are replaced by a rabbit-like hopping gait. The neuronal mechanism that is responsible for the gait switch in these KO mice is not known. Here, using intersectional genetics, we demonstrate that a spinal cord-specific deletion of EphA4 signaling is sufficient to generate the overground hopping gait. In contrast, selective deletion of EphA4 signaling in forebrain neurons, including the corticospinal tract neurons, did not result in a change in locomotor pattern. The gait switch was attributed to the loss of EphA4 signaling in excitatory Vglut2+neurons, which is accompanied by an increased midline crossing of Vglut2+neurons in the ventral spinal cord. Our findings functionally define spinal EphA4 signaling in excitatory Vglut2+neurons as required for proper organization of the spinal locomotor circuitry, and place these cells as essential components of the mammalian locomotor network. |
| Databáze: | OpenAIRE |
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