Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling
| Autor: | Shawn B. Frost, Rylan S. Larsen, Tharkika Nagendran, Randolph J. Nudo, Anne Marion Taylor, Rebecca L. Bigler, Benjamin D. Philpot |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Dendritic spine medicine.medical_treatment Gene Expression General Physics and Astronomy Hindlimb Rats Sprague-Dawley 0302 clinical medicine Spinal cord contusion Axon lcsh:Science 0303 health sciences Neuronal Plasticity Multidisciplinary Chemistry Pyramidal Cells Motor Cortex Axotomy Anatomy Microfluidic Analytical Techniques Netrin-1 medicine.anatomical_structure Trans-synaptic signaling Nerve tract Motor cortex Science Dendritic Spines Primary Cell Culture Glutamic Acid Biology Inhibitory postsynaptic potential Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Cellular neuroscience medicine Animals Spinal Cord Injuries 030304 developmental biology fungi General Chemistry Embryo Mammalian 030104 developmental biology nervous system Synapses Synaptic plasticity lcsh:Q Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-16 (2017) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-017-00652-y |
| Popis: | Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling. Spinal cord injury can induce synaptic reorganization and remodeling in the brain. Here the authors study how severed distal axons signal back to the cell body to induce hyperexcitability, loss of inhibition and enhanced presynaptic release through netrin-1. |
| Databáze: | OpenAIRE |
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