Intrinsic Homeostatic Plasticity in Mouse and Human Sensory Neurons

The nervous system has a tremendous capacity for experience-dependent plasticity. In response to changes in activity induced by environmental cues, many types of neurons undergo a process known as homeostatic plasticity, which serves to maintain overall network function in the face of mounting experience-dependent changes in synaptic strengths. Homeostatic plasticity involves both 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 both animal models and in human patients. However, it is not known whether homeostatic plasticity is engaged in sensory neurons under normal conditions or whether dysfunction in these homeostatic mechanisms might contribute to the pathophysiology of chronic pain. To address these questions, we tested the impact of sustained depolarization on various measures of excitability in mouse and human sensory neurons. Depolarization induced by 30mM KCl induces a compensatory decrease in the excitability of both mouse and human sensory neurons. Moreover, we also find that voltage-gated sodium currents are robustly inhibited in mouse sensory neurons after chronic depolarization, thus contributing to the overall decrease in neuronal excitability and serving as a potential regulatory mechanism to drive intrinsic neuronal homeostatic control. Our results indicate that mouse and human sensory neurons undergo homeostatic regulation of intrinsic excitability in response to sustained depolarization. Decreased efficacy of these homeostatic mechanisms could potentially contribute to the development of pathological conditions, including chronic pain. Overall design: To investigate changes at whole transcriptome level for cultured human and mouse neurons after sustained depolarization. We compared gene expression across 3 treatment conditions: 24h KCl, 24h KCl followed by 24h recovery in control media, and control media. Each condition has 3 replicates.