Abstract

Dopamine (DA) modulates the activity of nuclei within the ascending and descending auditory pathway. Previous studies have identified neurons and fibers in the inferior colliculus (IC) which are positively labeled for tyrosine hydroxylase (TH), a key enzyme in the synthesis of dopamine. However, the origins of the tyrosine hydroxylase positive projections to the inferior colliculus have not been fully explored. The lateral lemniscus (LL) provides a robust inhibitory projection to the inferior colliculus and plays a role in the temporal processing of sound. In the present study, immunoreactivity for tyrosine hydroxylase was examined in animals with and without 6-hydroxydopamine (6-OHDA) lesions. Lesioning, with 6-OHDA placed in the inferior colliculus, led to a significant reduction in tyrosine hydroxylase immuno-positive labeling in the lateral lemniscus and inferior colliculus. Immunolabeling for dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT), enzymes responsible for the synthesis of norepinephrine (NE) and epinephrine (E), respectively, were evaluated. Very little immunoreactivity for DBH and no immunoreactivity for PNMT was found within the cell bodies of the dorsal, intermediate, or ventral nucleus of the lateral lemniscus. The results indicate that catecholaminergic neurons of the lateral lemniscus are likely dopaminergic and not noradrenergic or adrenergic. Next, high-pressure liquid chromatography (HPLC) analysis was used to confirm that dopamine is present in the inferior colliculus and nuclei that send projections to the inferior colliculus, including the cochlear nucleus (CN), superior olivary complex (SOC), lateral lemniscus, and auditory cortex (AC). Finally, fluorogold, a retrograde tracer, was injected into the inferior colliculus of adult rats. Each subdivision of the lateral lemniscus contained fluorogold within the somata, with the dorsal nucleus of the lateral lemniscus showing the most robust projections to the inferior colliculus. Fluorogold-tyrosine hydroxylase colocalization within the lateral lemniscus was assessed. The dorsal and intermediate nuclei neurons exhibiting similar degrees of colocalization, while neurons of the ventral nucleus had significantly fewer colocalized fluorogold-tyrosine hydroxylase labeled neurons. These results suggest that several auditory nuclei that project to the inferior colliculus contain dopamine, dopaminergic neurons in the lateral lemniscus project to the inferior colliculus and that dopaminergic neurotransmission is poised to play a pivotal role in the function of the inferior colliculus.

Highlights

  • Dopamine (DA) is a neuromodulatory neurotransmitter in the brain that is involved in several processes, such as cognition, motor function, motivation, and processing of stimuli from sensory systems, including the auditory system

  • Previous studies have reported on the production of tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis, within the inferior colliculus (IC) (Paloff and Usunoff, 2000; Holt et al, 2005) with many TH immunolabeled terminals negative for dopamine β-hydroxylase (DBH) or phenylethanolamine N-methyltransferase (PNMT), enzymes that are absent in catecholaminergic neurons that produce DA (Fyk-Kolodziej et al, 2015)

  • TH immunoreactivity was evaluated in the IC and lateral lemniscus (LL) of both non-lesioned animals and animals lesioned after delivery of 6-OHDA to the IC

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Summary

Introduction

Dopamine (DA) is a neuromodulatory neurotransmitter in the brain that is involved in several processes, such as cognition, motor function, motivation, and processing of stimuli from sensory systems, including the auditory system. DA has been found to modulate the activity of IC neurons in response to auditory stimuli (Gittelman et al, 2013), and DA receptor modulation has been shown to alter auditory-stimulated IC responses within a behavioral context (Satake et al, 2012; Muthuraju et al, 2014). These studies suggest that DA in the IC modulates the processing of auditory stimuli. The origin(s) of DA within the IC remain unclear

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