Faculty, Staff and Student Publications
Language
English
Publication Date
1-6-2025
Journal
The Journal of General Physiology
DOI
10.1085/jgp.202313488
PMID
39688836
PMCID
PMC11651306
PubMedCentral® Posted Date
12-17-2024
PubMedCentral® Full Text Version
Post-print
Abstract
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 of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory changes that decrease the excitability of mouse and human sensory neurons without directly opposing membrane depolarization. Voltage-clamp recordings show that sustained depolarization produces no significant alteration in voltage-gated potassium currents, but a robust reduction in voltage-gated sodium currents, likely contributing to the overall decrease in neuronal excitability. The compensatory decrease in neuronal excitability and reduction in voltage-gated sodium currents reversed completely following a 24-h recovery period in a normal medium. Similar adaptive changes were not observed in response to 24 h of sustained action potential firing induced by optogenetic stimulation at 1 Hz, indicating the need for prolonged depolarization to drive engagement of this adaptive mechanism in sensory neurons. Our findings show that mouse and human sensory neurons are capable of engaging adaptive mechanisms to regulate intrinsic excitability in response to sustained depolarization in a manner similar to that described in neurons in the central nervous system.
Keywords
Sensory Receptor Cells, Adaptation, Physiological, Humans, Animals, Mice, Ganglia, Spinal, Cells, Cultured, Male, Female, Child, Preschool, Child, Adolescent, Young Adult, Adult, Gene Expression Profiling, Electrophysiology, Neuronal Plasticity
Published Open-Access
yes
Recommended Citation
McIlvried, Lisa A; Del Rosario, John Smith; Pullen, Melanie Y; et al., "Intrinsic Adaptive Plasticity in Mouse and Human Sensory Neurons" (2025). Faculty, Staff and Student Publications. 6521.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6521
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