Ca²⁺-activated K⁺channels reduce network excitability, improving adaptability and energetics for transmitting and perceiving sensory information

AbstractCa2+-activated K+channels (BK and SK) are ubiquitous in synaptic circuits, but their role in network adaptation and sensory perception remains largely unknown. Using electrophysiological and behavioral assays and biophysical modelling, we discover how visual information transfer in mutants lacking the BK channel (dSlo−), SK channel (dSK−) or both (dSK−;;dSlo−) is shaped in the female fruit fly (Drosophila melanogaster) R1-R6 photoreceptor-LMC circuits (R-LMC-R system) through synaptic feedforward-feedback interactions and reduced R1-R6ShakerandShabK+conductances. This homeostatic compensation is specific for each mutant, leading to distinctive adaptive dynamics. We show how these dynamics inescapably increase the energy cost of information and promote the mutants’ distorted motion perception, determining the true price and limits of chronic homeostatic compensation in anin vivogenetic animal model. These results reveal why Ca2+-activated K+channels reduce network excitability (energetics), improving neural adaptability for transmitting and perceiving sensory information.Significance statementIn this study, we directly linkin vivoandex vivoexperiments with detailed stochastically operating biophysical models to extract new mechanistic knowledge of howDrosophilaphotoreceptor-interneuron-photoreceptor (R-LMC-R) circuitry homeostatically retains its information sampling and transmission capacity against chronic perturbations in its ion-channel composition, and what is the cost of this compensation and its impact on optomotor behavior. We anticipate that this novel approach will provide a useful template to other model organisms and computational neuroscience, in general, in dissecting fundamental mechanisms of homeostatic compensation and deepening our understanding of how biological neural networks work.