1. Calcium plays an essential role in early-stage dendrite injury detection and regeneration
- Author
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Duarte, Vinicius N, Lam, Vicky T, Rimicci, Dario S, and Thompson-Peer, Katherine L
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Physical Injury - Accidents and Adverse Effects ,Traumatic Head and Spine Injury ,Regenerative Medicine ,1.1 Normal biological development and functioning ,Neurological ,Dendrites ,Animals ,Calcium ,Nerve Regeneration ,Humans ,Mice ,Potassium Channels ,Inwardly Rectifying ,Mice ,Transgenic ,Dendrite injury ,Dendrite repair ,Dendrite regeneration ,Drosophila ,Injury detection ,Psychology ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
Dendrites are injured in a variety of clinical conditions such as traumatic brain and spinal cord injuries and stroke. How neurons detect injury directly to their dendrites to initiate a pro-regenerative response has not yet been thoroughly investigated. Calcium plays a critical role in the early stages of axonal injury detection and is also indispensable for regeneration of the severed axon. Here, we report cell and neurite type-specific differences in laser injury-induced elevations of intracellular calcium levels. Using a human KCNJ2 transgene, we demonstrate that hyperpolarizing neurons only at the time of injury dampens dendrite regeneration, suggesting that inhibition of injury-induced membrane depolarization (and thus early calcium influx) plays a role in detecting and responding to dendrite injury. In exploring potential downstream calcium-regulated effectors, we identify L-type voltage-gated calcium channels, inositol triphosphate signaling, and protein kinase D activity as drivers of dendrite regeneration. In conclusion, we demonstrate that dendrite injury-induced calcium elevations play a key role in the regenerative response of dendrites and begin to delineate the molecular mechanisms governing dendrite repair.
- Published
- 2024