Distribution and phenotypes of unipolar brush cells in relation to the granule cell system of the rat cochlear nucleus

Abstract

In most mammals the cochlear nuclear complex (CN) contains a distributed system of granule cells (GCS), whose parallel fiber axons innervate the dorsal cochlear nucleus (DCN). Like their counterpart in cerebellum, CN granules are innervated by mossy fibers of various origins. The GCS is complemented by unipolar brush (UBCs) and Golgi cells, and by stellate and cartwheel cells of the DCN. This cerebellum-like microcircuit modulates the activity of the DCN's main projection neurons, the pyramidal, giant and tuberculoventral neurons, and is thought to improve auditory performance by integrating acoustic and proprioceptive information. In this paper, we focus on the rat UBCs, a chemically heterogeneous neuronal population, using antibodies to calretinin, metabotropic glutamate receptor 1alpha (mGluR1alpha), epidermal growth factor substrate 8 (Eps8) and the transcription factor T-box gene Tbr2 (Tbr2). Eps8 and Tbr2 labeled most of the CN's UBCs, if not the entire population, while calretinin and mGluR1alpha distinguished two largely separate subsets with overlapping distributions. By double labeling with antibodies to Tbr2 and the alpha6 GABA receptor A (GABAA) subunit, we found that UBCs populate all regions of the GCS and occur at remarkably high densities in the DCN and subpeduncular corner, but rarely in the lamina. Although GCS subregions likely share the same microcircuitry, their dissimilar UBC densities suggest they may be functionally distinct. UBCs and granules are also present in regions previously not included in the GCS, namely the rostrodorsal magnocellular portions of ventral cochlear nucleus, vestibular nerve root, trapezoid body, spinal tract and sensory and principal nuclei of the trigeminal nerve, and cerebellar peduncles. The UBC's dendritic brush receives AMPA- and NMDA-mediated input from an individual mossy fiber, favoring singularity of input, and its axon most likely forms several mossy fiber-like endings that target numerous granule cells and other UBCs, as in the cerebellum. The UBCs therefore, may amplify afferent signals temporally and spatially, synchronizing pools of target neurons.

Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1

“…Pax6 and Tbr2 (Eomes -Mouse Genome Informatics), markers for granule cells (Weedman et al, 1996;Yamasaki et al, 2001) and unipolar brush cells (Floris et al, 1994;Dino and Mugnaini, 2008), respectively, were not co-stained with β-gal in the DCN (Fig. 2H,I).…”

Auditory System

“…The granule cell system has been studied in great detail in rats (Figs. 3 and 4;Mugnaini et al, 1980;Wouterlood et al, 1984;Ohlrogge et al, 2001;Dunn et al, 2006;Diño and Mugnaini, 2008). The granule cell areas are so prominent in many species, like the rat, that they are considered by some to form a third CN division (for review, see Diño and Mugnaini, 2008), although its presence in cetacea and primates is debated (Osen and Jansen, 1965;Osen, 1979a, 1979b;Moore et al, 1996; but see Rubio et al, 2008).…”

“…3 and 4;Mugnaini et al, 1980;Wouterlood et al, 1984;Ohlrogge et al, 2001;Dunn et al, 2006;Diño and Mugnaini, 2008). The granule cell areas are so prominent in many species, like the rat, that they are considered by some to form a third CN division (for review, see Diño and Mugnaini, 2008), although its presence in cetacea and primates is debated (Osen and Jansen, 1965;Osen, 1979a, 1979b;Moore et al, 1996; but see Rubio et al, 2008). Because their axons converge on the molecular layer of the DC, the granule cells and their afferents are believed to form a functionally unique system within the CNC (Dunn et al, 1996;Oertel and Young, 2004) that is thought to improve auditory performance by integrating acoustic and proprioceptive information through unknown mechanism(s).…”

Cerebellum-Related Characteristics of Scn8a-Mutant Mice

“…The dorsal cochlear nucleus (DCoN) has a three-layered structure that shares several structural and functional characteristics with the cerebellar cortex [30][31][32]. The DCoN cartwheel cells show many similarities to the cerebellar Purkinje cells, including bursting, or complex spiking, activities [33][34][35][36].…”