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

Abstract

38Ca 2+ -activated K + channels (BK and SK) are ubiquitous in synaptic circuits, but their role in network 39 adaptation and sensory perception remains largely unknown. Using electrophysiological and 40 behavioral assays and biophysical modelling, we discover how visual information transfer in mutants 41 lacking the BK channel (dSlo -), SK channel (dSK -) or both (dSK -;;dSlo -) is shaped in the female fruit 42 fly (Drosophila melanogaster) R1-R6 photoreceptor-LMC circuits (R-LMC-R system) through 43 synaptic feedforward-feedback interactions and reduced R1-R6 Shaker and Shab K + conductances. 44 This homeostatic compensation is specific for each mutant, leading to distinctive adaptive dynamics. 45 We show how these dynamics inescapably increase the energy cost of information and promote the 1 mutants' distorted motion perception, determining the true price and limits of chronic homeostatic 2 compensation in an in vivo genetic animal model. These results reveal why Ca 2+ -activated K + 3 channels reduce network excitability (energetics), improving neural adaptability for transmitting and 4 perceiving sensory information. 5 6Significance statement: 7 In this study, we directly link in vivo and ex vivo experiments with detailed stochastically operating 8 biophysical models to extract new mechanistic knowledge of how Drosophila photoreceptor-9interneuron-photoreceptor (R-LMC-R) circuitry homeostatically retains its information sampling and 10 transmission capacity against chronic perturbations in its ion-channel composition, and what is the 11 cost of this compensation and its impact on optomotor behavior. We anticipate that this novel 12 approach will provide a useful template to other model organisms and computational neuroscience, 13 in general, in dissecting fundamental mechanisms of homeostatic compensation and deepening our 14 understanding of how biological neural networks work. 15 16 2018). Here, we study to what extent intrinsic perturbations of missing one or both of these K + 1 channels, through gene-deletion, can be neutralized by homeostatic processes trying to sustain 2 normal network functions, and what is the price of this compensation. 3 4By using electrophysiological and behavioral assays and biophysical modelling, we uncover why 5 Ca 2+ -activated K + channels improve communication between photoreceptors and Large Monopolar 6 Cells (LMCs), which in the fly eye lamina network form stereotypical columns of feedforward and 7 feedback synapses (R-LMC-R system) that process and route visual information to the fly brain. We 8show that although the loss of SK and BK channels does not diminish Drosophila photoreceptors' 9 information sampling capacity in vivo, it homeostatically reduces other K + currents and overloads 10 synaptic-feedback from the lamina network. This makes communication between the mutant 11 photoreceptors and LMCs inefficient, consuming more energy and distorting visual information flow 12 to the brain. Thus, homeostatic compensation of missing SK and BK channels within the lami...

Binocular Mirror-Symmetric Microsaccadic Sampling EnablesDrosophilaHyperacute 3D-Vision

“…WT flies #1-3), sometimes considerably. Therefore, it is not inconceivable that Drosophila's intrinsic/diurnal activity state, via feedback synapses from the higher brain centers (30,32), could co-regulate R1-R7/8-microsaccade gain, similar to what has already been shown for R1-R6 photoreceptor voltage responses (20,33,35,36,78,79).…”

“…Therefore, in light of all this evidence, together with Drosophila's striking hyperacute visual behaviors in a flight simulator system (11, 78) (Section V, below) and faster intracellular voltage responses (22,(33)(34)(35)(36)(77)(78)(79), we are confident that we present reliable and conservative estimates (lower bounds) of the L2terminals' motion direction-sensitive hyperacuity (for the given experimental conditions, instrumental noise, and sampling limitations). A freely flying Drosophila's visual acuity can only be better in natural environments and could even be significantly higher.…”

“…Other predictable observations indicate synaptic feedback modulating R1-R7/8 microsaccades:  dSK mutants' microsaccades (Fig. S29B) were faster and smaller than those of the wild-type flies, consistent with their accelerated photoreceptor voltage responses (78,79). dSK mutant R1-R6 photoreceptors have been shown to experience a tonic synaptic feedback overload from the lamina visual interneurons, which continuously depolarize them, making their voltage responses smaller and faster.…”

“…But it may also partly signify synaptic feedback strength (20,33,35,36,78) -top-down signaling from the brain (42), reflecting each fly's intrinsic activity state or attentiveness during the experiments. Thus, for example, dSK-mutants' intracellular R1-R6 voltage responses are faster and smaller than wild-type flies because they receive tonic feedback overload from visual interneurons (78,79). Correspondingly, their photoreceptor microsaccades are also faster and smaller (see Section II.8.i.…”

“…In the subsequent (biophysically tractable) four-parameter photon sampling model simulations (11,39,40), the light inputs were converted to refractory quantum bumps (QBs), which integrated each R1-R7/8's light-induced current (LIC). The photoreceptor voltage output simulations were then converted from their LICs (11,39,40) by using the Hodgkin-Huxley-type photoreceptor membrane model (78,95) (the HH-model module (11,39,40)).  Complex stimulus pattern simulations.…”