Small-conductance calcium-activated potassium (SK) channels are highly expressed in the central nervous system of different animal species, from humans to fruit flies. SK channels are essential regulators of neuronal functions that include excitability, firing frequency, synaptic transmission, and synaptic plasticity. However, studies on SK channels have been limited to ex vivo studies and pharmacological studies in animal models that have multiple SK isoforms. Therefore, in the absence of suitable animal models, the contribution of SK channels to neuronal function in complex circuits underlying sensory processing and behavior is largely unknown. Drosophila melanogaster has a single highly conserved SK gene ( dSK) simplifying the genetic analysis of SK function in vivo. We thus use Drosophila as an animal model to provide the first in vivo analysis of SK function in sensory processing and behavior.

Our first major study investigates the in vivo role of dSK in early visual processing. We combine genetics with electrophysiology to show that, in the eye, dSK encodes a highly conserved calcium-activated potassium current. We also demonstrate that dSK contributes to photoreceptor function by fine tuning synaptic transmission in the lamina circuits, the first visual synaptic network. Furthermore, our findings provide an example on how the inherent robustness and plasticity of homeostatically balanced networks can compensate for missing ion channels to maintain proper neural coding. Finally, we also investigate the in vivo contribution of the Drosophila large-conductance calcium-activated potassium channel (dSlo) to photoreceptor and retinal responses. We propose that, similar to dSK, dSlo plays an important role in visual processing by regulating synaptic transmission in the retinal circuitry.

Taking advantage of our dSK tools and the well-characterized courtship memory assay, our second study investigates the in vivo role of dSK in behavioral memory. Our data suggest that while dSK negatively regulates the acquisition of short-term memory 30min after a single training session, it is required for normal long-term memory 24h after spaced training. We provide evidence that the roles of dSK in courtship memory likely map to non-overlapping sets of neurons. Our findings suggest that SK channels can mediate multiple forms of behavioral plasticity by modulating the activity of different neuronal subtypes.