Dorsal cochlear nuclei microgliosis and circuit imbalance in rat tinnitus models

Although tinnitus origins are still elusive, hyperactivation of cochlear nuclei appears necessary in its early stages, especially in the dorsal nucleus (DCN), which displays changes in its cerebellar-like interneuronal network (Middleton et al 2011). Remodeling of the first CNS station is also observed in chronic pain and in gustatory nerve lesions, in both cases associated to microgliosis (Milligan et al. 2008, Benson 2012), consistently with a major role of microglia regulating circuit excitability in physiological and pathological states (Eyo and Dailey 2013). Although still incompletely characterized, microglia actions in regulating excitability include effects on both excitatory and inhibitory synapses (Ferrini and de Koninck, 2013). In our experiments we induced tinnitus by cochlear damage and salicylate injection, and found an increase in microglial density for both treatments, especially for cochlear damage, where microgliosis was seen both ipsilaterally (where auditory nerve degeneration occurred) and contralaterally (where no degeneration in afferents was present). Microglial morphology was clearly ameboid in ipsilateral cochlear damage DCN and ramified in other conditions. Microglia density variations were aligned with cochlear nuclei structures, and a focus of microgliosis was observed in the granular cap. A cell-type realistic network model of the dorsal cochlear nucleus was built from literature data. Several circuital parameters known to change in tinnitus (Bender and Trussell 2011, Li et al. 2013) and be affected by microglia (Ferrini and de Koninck, 2013) were changed accordingly to local microgliosis strength, and the effects of these changes on fusiform cells output was observed.