Presentation/Session Information

Session Information

Session Title: Behavior Session Type: Parallel
Session Location: De Neve Auditorium Session Time: Thu, Jun 25 8:30AM - 11:30AM

Presentation Information

Program Number: 45 Presentation Time: 10:54AM - 11:06AM

Presentation Content

The ciliary protein, EFHC1, implicated in epilepsy, functions at the cilium and synapse to modulate dopamine signalling.C.M. Loucks 1, A.H. McEwan 2, T.A. Timbers 1, C.M. Li 1, D.S. Walker 3, J.L. Johnson 1, W.R. Schafer 3, C.H. Rankin 2,4, M.R. Leroux 1. 1)Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada; 2)Brain Research Centre, University of British Columbia, Vancouver, BC, Canada; 3)Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, UK; 4)Department of Psychology, University of British Columbia, Vancouver, BC, Canada

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.

Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

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