Vollum Institute and Oregon Hearing Research Center, Oregon Health & Science University, Portland, Oregon 97239.
Vollum Institute and Oregon Hearing Research Center, Oregon Health & Science University, Portland, Oregon 97239
J Neurosci. 2022 Apr 20;42(16):3381-3393. doi: 10.1523/JNEUROSCI.1190-21.2022. Epub 2022 Mar 10.
The dorsal cochlear nucleus (DCN) integrates auditory nerve input with nonauditory sensory signals and is proposed to function in sound source localization and suppression of self-generated sounds. The DCN also integrates activity from descending auditory pathways, including a particularly large feedback projection from the inferior colliculus (IC), the main ascending target of the DCN. Understanding how these descending feedback signals are integrated into the DCN circuit and what role they play in hearing requires knowing the targeted DCN cell types and their postsynaptic responses. In order to explore these questions, neurons in the DCN that received descending synaptic input from the IC were labeled with a trans-synaptic viral approach in male and female mice, which allowed them to be targeted for whole-cell recording in acute brain slices. We tested their synaptic responses to optogenetic activation of the descending IC projection. Every cell type in the granule cell domain received monosynaptic, glutamatergic input from the IC, indicating that this region, considered an integrator of nonauditory sensory inputs, processes auditory input as well and may have complex and underappreciated roles in hearing. Additionally, we found that DCN cell types outside the granule cell regions also receive descending IC signals, including the principal projection neurons, as well as the neurons that inhibit them, leading to a circuit that may sharpen tuning through feedback excitation and lateral inhibition. Auditory processing starts in the cochlea and ascends through the dorsal cochlear nucleus (DCN) to the inferior colliculus (IC) and beyond. Here, we investigated the feedback projection from IC to DCN, whose synaptic targets and roles in auditory processing are unclear. We found that all cell types in the granule cell regions, which process multisensory feedback, also process this descending auditory feedback. Surprisingly, all except one cell type in the entire DCN receive IC input. The IC-DCN projection may therefore modulate the multisensory pathway as well as sharpen tuning and gate auditory signals that are sent to downstream areas. This excitatory feedback loop from DCN to IC and back to DCN could underlie hyperexcitability in DCN, widely considered an etiology of tinnitus.
背侧耳蜗核 (DCN) 将听觉神经输入与非听觉感觉信号整合在一起，据推测其功能在于声源定位和抑制自体产生的声音。DCN 还整合了来自下行听觉通路的活动，包括来自下丘 (IC) 的特别大的反馈投射，IC 是 DCN 的主要上行靶标。要了解这些下行反馈信号如何整合到 DCN 回路中以及它们在听觉中起什么作用，就需要了解靶向 DCN 细胞类型及其突触后反应。为了探索这些问题，我们使用跨突触病毒方法在雄性和雌性小鼠中标记了从 IC 接收下行突触输入的 DCN 神经元，这使得它们可以在急性脑切片中进行全细胞记录。我们测试了它们对下行 IC 投射光遗传学激活的突触反应。颗粒细胞域中的每个细胞类型都从 IC 接收单突触谷氨酸能输入，这表明这个被认为是非听觉感觉输入整合器的区域也处理听觉输入，并且可能在听觉中具有复杂且未被充分认识的作用。此外，我们发现颗粒细胞区域以外的 DCN 细胞类型也接收来自 IC 的下行 IC 信号，包括主要投射神经元以及抑制它们的神经元，从而形成一个可能通过反馈兴奋和侧向抑制来锐化调谐的回路。听觉处理始于耳蜗，并通过背侧耳蜗核 (DCN) 上升到下丘 (IC) 及更远的地方。在这里，我们研究了来自 IC 到 DCN 的反馈投射，其突触靶标和在听觉处理中的作用尚不清楚。我们发现，处理多感觉反馈的颗粒细胞区域中的所有细胞类型也处理这种下行听觉反馈。令人惊讶的是，整个 DCN 中除了一种细胞类型外，其余所有细胞类型都接收 IC 输入。因此，IC-DCN 投射可能会调节多感觉通路，并锐化调谐和门控传递到下游区域的听觉信号。这种来自 DCN 到 IC 再回到 DCN 的兴奋性反馈回路可能是 DCN 过度兴奋的基础，DCN 被广泛认为是耳鸣的病因。
