Abstract
Despite the importance of our sense of balance we still know remarkably little about the central control of the peripheral balance system. While previous work has shown that activation of the efferent vestibular system results in modulation of afferent vestibular neuron discharge, the intrinsic and synaptic properties of efferent neurons themselves are largely unknown. Here we substantiate the location of the efferent vestibular nucleus (EVN) in the mouse, before characterizing the input and output properties of EVN neurons in vitro. We made transverse serial sections through the brainstem of 4-week-old mice, and performed immunohistochemistry for calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT), both expressed in the EVN of other species. We also injected fluorogold into the posterior canal and retrogradely labelled neurons in the EVN of ChAT:: tdTomato mice expressing tdTomato in all cholinergic neurons. As expected the EVN lies dorsolateral to the genu of the facial nerve (CNVII). We then made whole-cell current-, and voltage-clamp recordings from visually identified EVN neurons. In current-clamp, EVN neurons display a homogeneous discharge pattern. This is characterized by a high frequency burst of action potentials at the onset of a depolarizing stimulus and the offset of a hyperpolarizing stimulus that is mediated by T-type calcium channels. In voltage-clamp, EVN neurons receive either exclusively excitatory or inhibitory inputs, or a combination of both. Despite this heterogeneous mixture of inputs, we show that synaptic inputs onto EVN neurons are predominantly excitatory. Together these findings suggest that the inputs onto EVN neurons, and more specifically the origin of these inputs may underlie EVN neuron function.
Highlights
Our sense of balance is fundamental to our ability to interact with our environment, yet central nervous control of peripheral vestibular activity remains poorly understood
The location of the efferent vestibular nucleus (EVN) was determined by immunohistochemical labelling using antibodies against calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT)
In order to investigate the intrinsic and synaptic electrophysiological properties of efferent vestibular nucleus neurons we sought to confirm the location of the EVN using CGRP and ChAT immunohistochemistry as well as direct retrograde tracing from the vestibular periphery
Summary
Our sense of balance is fundamental to our ability to interact with our environment, yet central nervous control of peripheral vestibular activity remains poorly understood. Intrinsic and Synaptic Profiles of EVN Neurons labyrinth receives dual innervation: the afferent component relays information regarding linear and rotational motion of the head from the periphery to the brainstem, and the efferent division which originates in the brainstem and terminates on vestibular hair cells and primary afferents. These efferent neurons have been shown to exert direct inhibitory modulatory control over type II hair cells [1,2,3], and direct excitatory control of afferent nerve fibres contacting both type I and type II hair cells [4,5,6]. Efferent neurons bifurcate extensively, allowing for a single efferent fibre to innervate more than one vestibular end organ and exert influence over hair-cell/afferent signalling in multiple planes of head motion [10, 13,14,15,16]
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