Understanding tinnitus: The dorsal cochlear nucleus, organization and plasticity

Abstract

Tinnitus, the perception of a phantom sound, is a common consequence of damage to the auditory periphery. A major goal of tinnitus research is to find the loci of the neural changes that underlie the disorder. Crucial to this endeavor has been the development of an animal behavioral model of tinnitus, so that neural changes can be correlated with behavioral evidence of tinnitus. Three major lines of evidence implicate the dorsal cochlear nucleus (DCN) in tinnitus. First, elevated spontaneous activity in the DCN is correlated with peripheral damage and tinnitus. Second, there are somatosensory inputs to the DCN that can modulate spontaneous activity and might mediate the somatic-auditory interactions seen in tinnitus patients. Third, we have found a subpopulation of DCN neurons in the adult rat that express doublecortin, a plasticity-related protein. The expression of this protein may reflect a role of these neurons in the neural reorganization causing tinnitus. However, there is a problem in extending the findings in the rodent DCN to humans. Classic studies state that the structure of the primate DCN is quite different from that of rodents, with primates lacking granule cells, the recipients of somatosensory input. To address the possibility of major species differences in DCN organization, we compared Nissl-stained sections of the DCN in five different species. In contrast to earlier reports, our data suggest that the organization of the primate DCN is not dramatically different from that of the rodents, and validate the use of animal data in the study of tinnitus.

Glutamic acid decarboxylase levels in the cochlear nucleus of rats with acoustic trauma-induced chronic tinnitus

“…This suggests that neuroplastic changes could be responsible for long-term alterations and the persistence of tinnitus in the chronic condition [15]. Previous research has demonstrated that a reorganisation of the DCN occurs following acoustic trauma [3]. These plastic changes could be a response to a new equilibrium being established as communication is altered from the auditory periphery [8].…”

“…In addition, evidence of reduced GABAergic inhibition and increased spontaneous activity has also been found in the dorsal cochlear nucleus (DCN) of mice with behaviour signs of tinnitus [11]. Since the CN is the first region of the CNS to receive and process auditory information, it occupies an pivotal role in the generation of tinnitus [3]. The dorsal cochlear nucleus (DCN), especially, has been proposed as a tinnitus trigger site [7].…”

Auditory System

“…There are several lines of evidence that implicate the DC in tinnitus. These include: (1) the presence of elevated spontaneous activity in the DC which is correlated with peripheral damage and tinnitus; (2) the somatosensory inputs to the DC that can modulate spontaneous activity and might mediate the somatic-auditory interactions seen in tinnitus patients; and (3) the expression of doublecortin, a plasticity-related protein (for review, see Baizer et al, 2012). Recent data also implicate the VC, and in particular spherical bushy cells in tinnitus (Gu et al, 2012).…”

Brainstem projections to molecular layer heterotopia of the cerebellar vermis: Evidence from the Allen Mouse Brain Connectivity Database

“…The cochlear group of nuclei constituent an important part of the auditory brainstem system which is critical for sound localization/processing and has been implicated in hearing disorders such as tinnitus [15]. Projections from the dorsal cochlear nuclei (DCN) in particular, have been demonstrated after retrograde tracer injection into the posterior vermis [16].…”