Aerial respiratory behavior in Lymnaea was operantly conditioned so that the animals perform aerial respiration significantly less often. Using the standard training procedure (pond water made hypoxic by bubbling N 2 through it) both food-deprived and fed animals learned and exhibited long-term memory (LTM). However, food-deprived animals exhibited neither learning nor memory when trained under a condition in which the hypoxic pond water also contained a food odorant (carrot, the food-odorant procedure). Fed animals, however, learned and exhibited LTM with the food-odorant procedure. Thus, the presence of the food odorant per se did not prevent learning or the establishment of LTM. Further experimentation, however, revealed that the ability of the snails to have recall (i.e., memory) for the learned behavior was dependent on the context in which memory was tested. That is, if animals were trained with the food-odorant procedure they could only exhibit recall if tested in the food-odorant context and vice versa with the standard training procedure. Thus, although fed animals could learn and show LTM with either training and testing procedure, LTM could only be seen when they were tested in the context in which they were trained.

Voltage- and calcium-dependent BK channels regulate calcium-dependent cellular events such as neurotransmitter release by limiting calcium influx. Their plasma membrane abundance is an important factor in determining BK current and thus regulation of calcium-dependent events. In C. elegans, we show that ERG-28, an endoplasmic reticulum (ER) membrane protein, promotes the trafficking of SLO-1 BK channels from the ER to the plasma membrane by shielding them from premature degradation. In the absence of ERG-28, SLO-1 channels undergo aspartic protease DDI-1-dependent degradation, resulting in markedly reduced expression at presynaptic terminals. Loss of erg-28 suppressed phenotypic defects of slo-1 gain-of-function mutants in locomotion, neurotransmitter release, and calcium-mediated asymmetric differentiation of the AWC olfactory neuron pair, and conferred significant ethanol-resistant locomotory behavior, resembling slo-1 loss-of-function mutants, albeit to a lesser extent. Our study thus indicates that the control of BK channel trafficking is a critical regulatory mechanism for synaptic transmission and neural function.DOI: http://dx.doi.org/10.7554/eLife.24733.001

Voltage-and calcium-dependent BK channels regulate calcium-dependent cellular events such as neurotransmitter release by limiting calcium influx. Their plasma membrane abundance is an important factor in determining BK current and thus regulation of calciumdependent events. In C. elegans, we show that ERG-28, an endoplasmic reticulum (ER) membrane protein, promotes the trafficking of SLO-1 BK channels from the ER to the plasma membrane by shielding them from premature degradation. In the absence of ERG-28, SLO-1 channels undergo aspartic protease DDI-1-dependent degradation, resulting in markedly reduced expression at presynaptic terminals. Loss of erg-28 suppressed phenotypic defects of slo-1 gain-of-function mutants in locomotion, neurotransmitter release, and calcium-mediated asymmetric differentiation of the AWC olfactory neuron pair, and conferred significant ethanol-resistant locomotory behavior, resembling slo-1 loss-of-function mutants, albeit to a lesser extent. Our study thus indicates that the control of BK channel trafficking is a critical regulatory mechanism for synaptic transmission and neural function.