Department of Pharmacology and Therapeutics, University of Florida School of Medicine, Gainesville, FL, United States.
Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, United States.
Front Neural Circuits. 2021 Mar 5;15:624563. doi: 10.3389/fncir.2021.624563. eCollection 2021.
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.
多巴胺（DA）调节着上行和下行听觉通路核团的活动。先前的研究已经确定了在下丘脑中（IC）中，对酪氨酸羟化酶（TH）呈阳性标记的神经元和纤维，酪氨酸羟化酶是多巴胺合成的关键酶。然而，酪氨酸羟化酶阳性投射到下丘脑中的起源尚未得到充分探索。外侧丘系（LL）对下丘脑提供了强大的抑制性投射，并在声音的时间处理中发挥作用。在本研究中，检查了具有和不具有 6-羟多巴胺（6-OHDA）损伤的动物中的酪氨酸羟化酶免疫反应性。在下丘脑中放置 6-OHDA 会导致外侧丘系和下丘脑中酪氨酸羟化酶免疫阳性标记物的显著减少。评估了多巴胺β-羟化酶（DBH）和苯乙醇胺-N-甲基转移酶（PNMT）的免疫标记，这两种酶分别负责去甲肾上腺素（NE）和肾上腺素（E）的合成。在外侧丘系的背核、中间核和腹核的细胞体中，很少发现 DBH 的免疫反应性，也没有 PNMT 的免疫反应性。结果表明，外侧丘系的儿茶酚胺能神经元可能是多巴胺能的，而不是去甲肾上腺素能或肾上腺素能的。接下来，使用高效液相色谱法（HPLC）分析来确认多巴胺存在于下丘脑中以及投射到下丘脑的核团中，包括耳蜗核（CN）、上橄榄复合体（SOC）、外侧丘系和听觉皮层（AC）。最后，将逆行示踪剂荧光金注入成年大鼠的下丘脑中。外侧丘系的每个细分部分都在细胞体中包含荧光金，其中外侧丘系的背核对下丘脑的投射最为强烈。评估了外侧丘系中荧光金-酪氨酸羟化酶的共定位。表现出相似程度共定位的背核和中间核神经元，而腹核神经元的共定位荧光金-酪氨酸羟化酶标记神经元明显较少。这些结果表明，投射到下丘脑的几个听觉核团含有多巴胺，外侧丘系的多巴胺能神经元投射到下丘脑，并且多巴胺能神经传递准备在下丘脑的功能中发挥关键作用。
