Department of Physics, Chemistry and Biology (IFM)

In the audio-vestibular system, the neurons responsible for carrying impulses from the sensory epithelium, in the cochlea for hearing and in the semicircular canals and otolith organs for balance, are called primary afferents. This neural code from the inner ear to the brain is also dynamically controlled by central nervous feedback to the audio-vestibular epithelium. The neurons responsible for this feedback are called efferents, and they carry impulses away from the central nervous system to the effectors. Although such efference provides the basis for a cognitive control of our hearing and balance, we still know surprisingly little about this feedback system.

My thesis is framed within a larger research project to understand what role this innervation of balance and hearing sensory organs from the brain play for our sensory experience. As a first aim, this project investigates the applicability of a transgenic mouse model, expressing GFP in cholinergic cells, for targeting the vestibular and olivocochlear efferent neurons, which are cholinergic. This targeting would enable us to perform electrophysiological experiments where, if expressing GFP,  the efferent neurons can be identified by eye in a fluorescence microscope. 

One known characteristics of the olivocochlear efferents is a transient outward current, also called A-type current, which leads to a delayed firing of action potentials ( Fujino et al., 1997). The Kv4 family of potassium channel subunits is responsible for this current ( Anderson et al., 2010). Now these currents have also been seen in preliminary experiments in vestibular efferents (Anna K Magnusson, unpublished data). Therefore the second aim with my thesis has been to investigate the presence of Kv4.2 and Kv4.3 subunits in the vestibular efferents, and also in olivocochlear efferents, since it is not known what subunits are expressed there.

The vestibular efferents have their cell bodies in the auditory brainstem, dorsolateral to the genu of the facial nerve (VII genu), close to the abduscens nucleus (VI). They project to the sensory hair cells in the vestibular system, where they make direct contact with the Type II peripheral hair cells and indirect contact with the Type I hair cells via the afferent nerve fibers or afferent terminals (Boyle and Highstein, 1990; Gacek, 1969). The olivocochlear efferents are divided into the medial olivocochlear efferents, called MOC, and the lateral olivocochlear efferents, called LOC. The medial olivocochlear (MOC) neurons are located around the medial superior olive (MSO) and the ventral periolivary zone and their axons make direct synapses with cochlear outer hair cells. The lateral olivocochlear (LOC) neurons are distributed within or around the lateral superior olive (LSO) and they project mainly to the spiral ganglion cell dendrites at the base of the cochlear inner hair cells (Warr and Guinan, 1979)

 The MOC neurons have been shown to control the outer hair cells in their role as cellular amplifiers (Ulfendahl and Flock, 1998) and to be involved in improving discrimination of complex sounds (Xiao and Suga, 2001). From recent experiments by Lieberman et al. it has been concluded that the LOC neurons are involved in adjusting the interaural sensitivity to sounds, which is the most important cue for sound localization (Darrow et al., 2006). There are many hypotheses about the VE neurons. One example is that they would reduce stimuli of self-generated motions to instead enhance biologically relevant sensations (Cullen and Minor, 2002). However, this hypothesis has been disproven and their functional role in balance remains elusive.