Cold-Temperature Coding with Bursting and Spiking Based on TRP Channel Dynamics in Drosophila Larva Sensory Neurons

Abstract

Temperature sensation involves thermosensitive TRP (thermoTRP) and non-TRP channels. Drosophila larval Class III (CIII) neurons serve as the primary cold nociceptors and express a suite of thermoTRP channels implicated in noxious cold sensation. How CIII neurons code temperature remains unclear. We combined computational and electrophysiological methods to address this question. In electrophysiological experiments, we identified two basic cold-evoked patterns of CIII neurons: bursting and spiking. In response to a fast temperature drop to noxious cold, CIII neurons distinctly mark different phases of the stimulus. Bursts frequently occurred along with the fast temperature drop, forming a peak in the spiking rate and likely coding the high rate of the temperature change. Single spikes dominated at a steady temperature and exhibited frequency adaptation following the peak. When temperature decreased slowly to the same value, mainly spiking activity was observed, with bursts occurring sporadically throughout the stimulation. The spike and the burst frequencies positively correlated with the rate of the temperature drop. Using a computational model, we explain the distinction in the occurrence of the two CIII cold-evoked patterns bursting and spiking using the dynamics of a thermoTRP current. A two-parameter activity map (Temperature, constant TRP current conductance) marks parameters that support silent, spiking, and bursting regimes. Projecting on the map the instantaneous TRP conductance, governed by activation and inactivation processes, reflects temperature coding responses as a path across silent, spiking, or bursting domains on the map. The map sheds light on how various parameter sets for TRP kinetics represent various types of cold-evoked responses. Together, our results indicate that bursting detects the high rate of temperature change, whereas tonic spiking could reflect both the rate of change and magnitude of steady cold temperature.

Neural substrates of cold nociception in Drosophila larva

“…Though we have not performed cold-evoked Ca2+ imaging of CIII md neurons in larval preparations without muscles, we have recorded electrical responses of CIII md neurons in the absence of muscle contractions using de-muscled larvae fillets to analyze cold-evoked firing patterns of CIII md neurons (Himmel et al, 2021, Himmel et al, 2023, Patel et al, 2022, Maksymchuk et al, 2022, Maksymchuk et al, 2023. These studies demonstrate the cold-evoked CIII neural activity is not dependent upon muscles.…”

“…To address potential confounds of cold-induced muscle contraction on cold-induced electrical activity of CIII md neurons, we performed these analyses on de-muscled fillets revealing that CIII neural activity is not dependent upon muscles in response to cold. Exposure to noxious cold stimuli results in temperature-dependent increases in CIII neuron firing pattern consisting of both bursting and tonic firing (Himmel et al, 2021, Himmel et al, 2023, Maksymchuk et al, 2022, Patel et al, 2022, Maksymchuk et al, 2023.…”