Aberrant dopamine signalling is associated with various forms of epilepsy. An important question is whether alterations in dopamine signalling contribute to epileptogenesis or are merely a consequence of increased neuronal excitability. In this work, we provide evidence for a direct link between the ciliary gene, EFHC1, commonly mutated in juvenile myoclonic epilepsy, and dopamine signalling. C. elegans EFHC1 localizes to a subset of ciliated dopaminergic neurons responsible for modulating specific behaviors based on food availability. In the presence of food, cilia are mechanically activated, leading to synaptic release of dopamine that is then able to modulate neuronal activity. EFHC1 is enriched at cilia, and we find that mechanosensory responses are disrupted in animals lacking EFHC1. Interestingly, EFHC1 also localizes to synapses, and mutations in EFHC1 cause phenotypes consistent with increased dopamine signalling due to spontaneous dopamine release at the synapse. This work shows that EFHC1 can modulate neuronal activity both at the cilium and the synapse. It also represents the first evidence that a gene implicated in epilepsy directly influences dopamine signalling and suggests a possible involvement of ciliary proteins in epileptogenesis.
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