title: Descending projections from the inferior colliculus to medial olivocochlear efferents: Mice with normal hearing, early onset hearing loss, and congenital deafness.
abstract: Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea to modulate incoming acoustic signals. Two groups of efferents have been described in mouse and this report will focus on the medial olivocochlear (MOC) system. Electrophysiological data suggest the MOC efferents function in selective listening by differentially attenuating auditory nerve fiber activity in quiet and noisy conditions. Because speech understanding in noise is impaired in age-related hearing loss, we asked whether pathologic changes in input to MOC neurons from higher centers could be involved. The present study investigated the anatomical nature of descending projections from the inferior colliculus (IC) to MOCs in 3-month old mice with normal hearing, and in 6-month old mice with normal hearing (CBA/CaH), early onset progressive hearing loss (DBA/2), and congenital deafness (homozygous Shaker-2). Anterograde tracers were injected into the IC and retrograde tracers into the cochlea. Electron microscopic analysis of double-labelled tissue confirmed direct synaptic contact from the IC onto MOCs in all cohorts. These labelled terminals are indicative of excitatory neurotransmission because they contain round synaptic vesicles, exhibit asymmetric membrane specializations, and are co-labelled with antibodies against VGlut2, a glutamate transporter. 3D reconstructions of the terminal fields indicate that in normal hearing mice, descending projections from the IC are arranged tonotopically with low frequencies projecting laterally and progressively higher frequencies projecting more medially. Along the mediolateral axis, the projections of DBA/2 mice with acquired high frequency hearing loss were shifted medially towards expected higher frequency projecting regions. Shaker-2 mice with congenital deafness had a much broader spatial projection, revealing abnormalities in the topography of connections. These data suggest that loss in precision of IC directed MOC activation could contribute to impaired signal detection in noise.
authors.affiliation: Hearing Research Unit, Neuroscience Division, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia; School of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, 2052, Australia. Electronic address: k.suthakar@student.unsw.edu.au.
authors.forename: Kirupa
authors.initials: K
authors.lastname: Suthakar
authors.affiliation: Hearing Research Unit, Neuroscience Division, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia; School of Medical Sciences, Faculty of Medicine, UNSW Australia, Sydney, NSW, 2052, Australia; Department of Otolaryngology, Head, Neck & Skull Base Surgery, St Vincent's Hospital, Sydney, NSW, 2010, Australia.
authors.forename: David K
authors.initials: DK
authors.lastname: Ryugo
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001306:Auditory Pathways / Q000503:physiopathology; D001307:Auditory Perception; D001522:Behavior, Animal; D003051:Cochlea / Q000294:innervation*; D003638:Deafness / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D020022:Genetic Predisposition to Disease; D006309:Hearing / Q000235:genetics; D007245:Inferior Colliculi / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009218:Myosins / Q000172:deficiency / Q000235:genetics; D056347:Neuroanatomical Tract-Tracing Techniques; D009847:Olivary Nucleus / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D010641:Phenotype; D017603:Signal Detection, Psychological; D013569:Synapses / Q000648:ultrastructure; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: C114013:Myo15 protein, mouse; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D009218:Myosins
keywords: Deafness; Descending; Hearing loss; Medial olivocochlear efferent; Tonotopy