Behavioral and Cellular Mechanisms Underlying Experience-Dependent Plasticity of Cold Nociception

The capacity for an organism to adapt to a constantly changing environment is fundamental for its ability to thrive, and ultimately, survive. The nervous system plays an important role in this response to the environment as it is responsible for both sensing external features of the environment and coordinating appropriate behavioral responses. While the overall organization and function of the nervous system are largely pre-determined, its capacity to adapt to environmental factors is essential for neural development and maintaining functional integrity. This experience-dependent plasticity is conserved across species as a critical underlying mechanism driving adaptive behaviors, physiological responses and changes in gene expression. Among sensory systems exhibiting plasticity, nociception is crucial for detecting dangerous or maladaptive environments, yet the plasticity of thermal nociception, particularly cold nociception, remains poorly understood. Building upon our laboratory’s work characterizing cold nociception in Drosophila melanogaster, we sought to determine the existence and extent of cold nociception plasticity as a result of short- and long-term thermal experience. We found that thermal rearing differentially regulates cold nociception: cooler conditions desensitize the nocifensive contraction response to noxious cold, whereas warmer conditions enhance cold nociceptive behavior. Transient noxious cold experience (CE) heightened contraction responses and increased precursor behaviors to noxious heat. These effects were recapitulated in fictive cold conditions via optogenetic activation of primary cold nociceptors (CIIIs), isolating neuronal contributions. Physiological recordings of CIII activity revealed that CE did not alter responses to noxious cold but sensitized neurons to typically innocuous cool, expanding their activation range. Rearing under noxious cold conditions altered CIII dendritic morphology, increasing branch density and number of filopodia, however transient CE was insufficient to do so. Physiological recordings revealed that CE did not alter responses to noxious cold but sensitized CIIIs to innocuous cool, expanding their activation range. Rearing in noxious cold conditions was sufficient to induce CIII dendritic complexity, whereas transient CE did not. These findings confirm the presence of cold nociception plasticity and show that experience-dependent modulation influences both behavior and its underlying neural mechanisms.