Dopaminergic projections of the subparafascicular thalamic nucleus to the auditory brainstem

Highlights

• The subparafascicular thalamic nucleus (SPF) sends dopaminergic projections to the superior olivary complex (SOC).

• The same cells in the SPF that project to the SOC also are projecting to the inferior colliculus.

• The SPF likely acts as a global modulator of auditory processing via dopamine.

Abstract

Neuromodulators can alter the response properties of sensory neurons, including those in the auditory system. Dopamine, which plays a major role in reward and movement, has been shown to alter neural responses in the auditory brainstem and midbrain. Recently we identified the subparafascicular thalamic nucleus (SPF), part of the A11 dopaminergic cell group, as the source of dopamine to the inferior colliculus (IC). The superior olivary complex (SOC) is also a likely target of dopaminergic projections from the SPF because it receives projections from the SPF and contains fibers and terminals immunoreactive for tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. However, it is unknown if the projections from the SPF to SOC are dopaminergic, and if single neurons in the SPF project to both the IC and SOC. Using anterograde tracing combined with fluorescent immunohistochemistry, we found that the SPF sends dopaminergic projections to the superior paraolivary nucleus and the medial nucleus of the trapezoid body, but not the lateral superior olive. We confirmed these projections using a retrograde tracer. By making dual retrograde deposits in the IC and SOC, we found that individual dopaminergic cells innervate both the IC and SOC. These results suggest dopaminergic innervation, likely released in a context dependent manner, occurs at multiple levels of the auditory pathway.

Introduction

Neuromodulatory systems have the ability to significantly alter auditory processing based on social context and internal state (Hurley and Hall, 2011, Ikeda et al., 2015). A variety of studies have provided intriguing data suggesting that the neuromodulator dopamine plays an important role in modulating auditory responses. For example, Bender et al. (2010) showed that dopamine can modulate action potential initiation in the dorsal cochlear nucleus and Gittelman et al. (2013) showed that dopamine heterogeneously modulates response properties of neurons in the inferior colliculus (IC). Moreover, people with Parkinson's disease and schizophrenia, both disorders characterized by a dysfunction in dopamine signaling, have speech processing problems (Gräber et al., 2002, Schröder et al., 2010, Kantrowitz et al., 2015) and people with schizophrenia may experience auditory hallucinations (Lennox et al., 2000). Thus, dopamine may be required for normal auditory processing.

The sources of dopamine in the auditory system, however, are not well understood. Recently, we discovered that the subparafascicular thalamic nucleus (SPF) is the source of the dopaminergic input to the IC (Nevue et al., 2016). The SPF is part of the A11 dopaminergic cell group and sends widespread dopaminergic projections to many structures in the brain (Takada et al., 1988, Takada, 1993). In addition to dopaminergic neurons, the SPF contains neurons that use GABA or various neuropeptides including substance P, enkephalin, and somatostatin (Moriizumi and Hattori, 1992, Sugimoto et al., 1984, Wamsley et al., 1980). The SPF receives projections from many auditory nuclei including the superior olivary complex, inferior colliculus, nuclei of the lateral lemniscus, and medial geniculate body, and therefore may act as a convergence center for auditory projections (LeDoux et al., 1985, Wang et al., 2006, Yasui et al., 1990). Studies in fish have also identified a dopaminergic cell group in the hypothalamus, likely a homolog to the SPF, which sends projections to auditory nuclei, the inner ear, and lateral line (Metcalfe et al., 1985, Bricaud et al., 2001, Forlano et al., 2014). Thus, it is likely that the SPF in mammals sends dopaminergic projections to other auditory nuclei besides the IC.

In particular, the superior olivary complex (SOC) is a likely target of dopaminergic projections from the SPF. The SOC is a group of brainstem nuclei that functions as a convergence center within the ascending and descending auditory pathway, and these different nuclei play important roles in both monaural and binaural processing (Thompson and Schofield, 2000, Oliver, 2000). While it is known that the SOC receives projections from the SPF (Yasui et al., 1992) and contains TH-positive fibers and terminals (Mulders and Robertson, 2001, Mulders and Robertson, 2005), it is not known whether the SPF projections are the dopaminergic source to the SOC. In addition, it is not known whether the same neurons in the SPF project to both the IC and SOC.

The purposes of this study were to determine 1) if the SPF sends dopaminergic projections to the SOC, and 2) whether individual neurons in the SPF project to both the auditory midbrain and brainstem. We first placed an anterograde tracer in the SPF and examined whether anterogradely labeled fibers in the SOC nuclei were colocalized with tyrosine hydroxylase (TH). We then confirmed the SPF to SOC projections by placing retrograde tracer deposits in the individual SOC nuclei. We found that the superior paraolivary nucleus (SPN) and medial nucleus of the trapezoid body (MNTB), but not the lateral superior olive (LSO), receive dopaminergic projections from the SPF. By placing different retrograde tracers in the SOC nuclei and the IC in the same animals, we also found that individual dopaminergic cells in the SPF project to both the IC and SOC. These results suggest that the SPF has the ability to alter auditory processing in multiple nuclei, potentially facilitating plasticity or altering ongoing responses to salient stimuli.