The nervous system generates a tremendous diversity of cell types that enable formation of functional neural circuits for information processing and mediating behaviors. Cellular diversity is especially important in the developing sensory system as it allows animals to detect different cues in the environment. However, the molecular mechanisms that generate neuronal diversification are not yet fully revealed. One way to generate cellular diversity in the nervous system is to specify different fates and functions of individual cell types across the left-right axis. Left-right asymmetry in the nervous system is present throughout the animal kingdom. The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes, AWCOFF and AWCON across the left-right axis. The default AWCOFF is specified by a Ca2+-regulated kinase cascade that is activated by influx of Ca2+ through the voltage-gated Ca2+ channel UNC-2/UNC-36. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes UNC-2/UNC-36 calcium channels in the future AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood.We show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that
slo-1 and
slo-2 act redundantly downstream of
nsy-5 to inhibit
unc-2/unc-36 Ca2+ signaling in the specification of AWCON.
nsy-5-dependent asymmetric expression of
slo-1/slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1/SLO-2 localize close to UNC-2 in AWC, consistent with functional coupling between these channels in AWC asymmetry. Furthermore,
slo-1/slo-2 regulate synaptic communication between AWC neurons to control AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal neuron differentiation.