Intrinsic adaptive plasticity in mouse and human sensory neurons. J Gen Physiol 2025 Jan 06;157(1)
Date
12/17/2024Pubmed ID
39688836Pubmed Central ID
PMC11651306DOI
10.1085/jgp.202313488Scopus ID
2-s2.0-85212890395 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
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.
Author List
McIlvried LA, Del Rosario JS, Pullen MY, Wangzhou A, Sheahan TD, Shepherd AJ, Slivicki RA, Lemen JA, Price TJ, Copits BA, Gereau RW 4thAuthor
Tayler D. Sheahan PhD Assistant Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptation, PhysiologicalAdolescent
Adult
Animals
Cells, Cultured
Child
Child, Preschool
Electrophysiology
Female
Ganglia, Spinal
Gene Expression Profiling
Humans
Male
Mice
Neuronal Plasticity
Sensory Receptor Cells
Young Adult
