Research paperDopaminergic projections of the subparafascicular thalamic nucleus to the auditory brainstem
Graphical abstract
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.
Section snippets
Animals
We used normal hearing (CBA/CaJ or C57BL/6J) adult mice less than 3 months old (Zheng et al., 1999, Kane et al., 2012) (9 males, 8 females) obtained from Jackson Laboratory or bred in our colony. All animals had free access to food and water and were on a reversed 12-h light/12-h dark schedule. All care and procedures were in accordance with the guidelines of the National Institutes of Health and were approved by the Washington State University Institutional Animal Care and Use Committee.
Preparation of animals for tracer injections
We
Results
To determine if the SPF sends dopaminergic projections to the SOC, we iontophoretically injected an anterograde tracer (10 K BDA) in the left SPF of 4 mice. The location of these deposits was confirmed after tissue processing (Fig. 1A). Neurons in the SPF have been shown previously to be dopaminergic and not noradrenergic (Takada et al., 1988, Koblinger et al., 2014, Nevue et al., 2016). By staining the same brains for TH, we determined if there were anterogradely labeled fibers in the SOC, and
Discussion
Dopamine has widespread effects on neurons, including altering how auditory neurons respond to sound (Gittelman et al., 2013). Surprisingly, the source(s) of dopamine in auditory nuclei has not been well studied. Recently, we described dopaminergic projections from the subparafascicular thalamic nucleus (SPF) to the inferior colliculus (IC) (Nevue et al., 2016). The purpose of this study was to determine if the SPF also provides dopaminergic input to the superior olivary nuclei (SOC). The SOC
Conclusion
Neuromodulation via dopamine is of interest throughout the auditory system from the inner ear to the cortex. In the inner ear, dopamine acts via D1 receptors at ribbon synapses to increase neurotransmission in sensory hair cells (Toro et al., 2015; Darrow et al., 2006). In the DCN, dopamine can modulate currents that mediate neuronal excitability (Bender et al., 2010), and it has heterogeneous (although largely depressive) effects on extracellular response properties in the IC (Gittelman
Author contributions
All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: AAN and CVP. Acquisition of data: AAN and RAF. Analysis and interpretation of data: AAN, RAF, and CVP. Drafting of the manuscript: AAN, RAF, and CVP.
Funding
This work was supported by NIDCD R01DC013102 to CVP.
Conflicts of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgements
We thank Cameron J. Elde for technical assistance.
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