title: Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses.
abstract: Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations.
authors.affiliation: Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Av. Brasília, Doca de Pedrouços, Lisbon 1400-038, Portugal. Electronic address: lauren.mcelvain@neuro.fchampalimaud.org.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McElvain
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Faulstich
authors.affiliation: Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Jeanne
authors.affiliation: Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Moore
authors.affiliation: Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, La Jolla, CA 92037, USA; Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: sascha@jhmi.edu.
authors.forename: Sascha
authors.initials: S
authors.lastname: du Lac
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D014725:Vestibular Nerve / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D002118:Calcium