title: Physiological characterization of vestibular efferent brainstem neurons using a transgenic mouse model.
abstract: The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential <-75 mV and their passive responses in the hyperpolarizing range. In contrast, the response properties of VE and LOC neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs.
authors.affiliation: Center for Hearing and Communication Research, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Unit of Audiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Leijon
authors.affiliation: Center for Hearing and Communication Research, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Unit of Audiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Magnusson
mesh_terms: D000200:Action Potentials; D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009476:Neurons, Efferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D014722:Vestibule, Labyrinth / Q000502:physiology
chemical_list: D002795:Choline O-Acetyltransferase