Age-dependent effects on sensory axonal excitability in normal mice

• Age-dependent changes occur on axonal excitability of both motor and sensory neurons. These changes may reflect alterations in passive membrane properties.
• Alterations of an ion conductance (e.g., H conductance) and cable properties (e.g., Barrett–Barrett conductance) explain the interval changes of sensory axonal excitability with maturation and aging.
• Dynamic changes of sensory axonal excitability may explain age-dependent sensory symptoms.

Serial recordings were performed to measure sensory excitability in peripheral nerves and elucidate age-dependent changes in neuronal ion currents in the peripheral sensory nervous system. The threshold tracking technique was used to measure multiple excitability indices in the tail sensory nerves of five normal male mice at four time points (6, 10, 14, and 19 weeks of age). A separate group of four mice was also measured at 43 weeks and at 60 weeks of age. Maturation was accompanied by an increase in early hyperpolarization and superexcitability at 10 weeks. At 60 weeks, the hyperpolarizing electrotonus shifted downward, while superexcitability became greater and subexcitability (double stimuli) decreased. Computer modeling showed that the most notable age-related interval changes in excitability parameters were Barrett–Barrett, H, and slow K+ conductances. Understanding age-related changes in the excitability of sensory axons may provide a platform for understanding age-dependent sensory symptoms and developing age-specific channel-targeting therapies.