Tinnitus Mouse Model

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Abstract

Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to the sources of the labeled terminals. VGLUT1 is associated with terminals of auditory nerve fibers, whereas VGLUT2 is associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig and rat have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. In order to confirm this hypothesis, knock-out studies in a mouse model of tinnitus
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1). The dorsal part of the cochlear nucleus (DCN) consists of a molecular layer, a fusiform cell layer, and a deep layer (abbreviated as DCN1, DCN2, and DCN3, respectively). The ventral part of the cochlear nucleus (VCN) is subdivided by a posterior and an anterior region (PVCN and AVCN, respectively). Furthermore, the area where the auditory nerve enters the nucleus can be defined as a separate region, which is called the interstitial region (INT; Lorente de Nó, 1933). The last region that is defined for the CN of the mouse is the granule cell lamina (GCL), which encapsulates the VCN on the dorsal and lateral side and consists mainly of granule and small cells. The CNcochlear nucleus (CN), which is the target of the VIIIth nerve, is the first auditory brain station where auditory input is integrated with input from other sensory modalities, such the somatosensory and the vestibular systems (Cant and Morest, 1978, Shore and Moore, 1998, Shore, 2005, Barker et al., 2012). Both VGLUT1 and VGLUT2 are highly expressed in the CN, with distinct distributions. Studies in guinea pig and rat have shown that these distinct expression profiles correspond to the source of the glutamatergic terminals (Zhou et al., 2007, Barker et al., 2012). VGLUT1 co-labels with synaptic terminals of type I auditory nerve fibers (ANFs) and is mostly expressed in the magnocellular region of the ventral CN (VCN) and the deep layer of the dorsal CN (DCN3) (Zhou et al., 2007, Gomez-Nieto and Rubio, 2009). On the other hand, VGLUT2 co-labels with non-auditory terminals, including those from the somatosensory and the vestibular system, and is mostly expressed in granule cell domainDCN2 and the small cell cap region (SCC), where these terminals primarily innervate granule cells (Haenggeli et al., 2005, Zhou et al.,

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