Intrinsic Homeostatic Plasticity in Mouse and Human Sensory Neurons.
Lisa A McIlvriedJohn Smith Del RosarioMelanie Y PullenAndi WangzhouTayler D SheahanAndrew J ShepherdRichard A SlivickiJohn A LemenTheodore John PriceBryan A CopitsRobert W GereauPublished in: bioRxiv : the preprint server for biology (2023)
In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons under normal conditions or altered after chronic pain is unknown. Here, we showed that sustained depolarization induced by 30mM KCl induces a compensatory decrease in the excitability in mouse and human sensory neurons. Moreover, voltage-gated sodium currents are robustly reduced in mouse sensory neurons contributing to the overall decrease in neuronal excitability. Decreased efficacy of these homeostatic mechanisms could potentially contribute to the development of the pathophysiology of chronic pain.
Keyphrases
- chronic pain
- spinal cord
- endothelial cells
- induced pluripotent stem cells
- transcranial direct current stimulation
- pluripotent stem cells
- end stage renal disease
- ejection fraction
- newly diagnosed
- peritoneal dialysis
- cerebrospinal fluid
- blood brain barrier
- working memory
- patient reported
- network analysis
- cerebral ischemia