Serotonin Regulation of VIP Interneurons and Auditory Learning

项目摘要 听觉知觉学习诱导听觉皮质(A1)的可塑性，这可以改善听力， 但触发这些变化的神经机制尚不清楚。跨感觉皮质区域，抑制 中间神经元正在成为可塑性调节的“守门人”，受到严格控制的平衡 刺激和抑制。皮质中间神经元群由许多细胞亚型组成。 以形态、生理和连通性区分的，表明存在几个不同的回路 可塑性调节。这些特定的中间神经元回路如何对皮质可塑性和感觉学习做出贡献 人们对此仍然知之甚少。 最近的工作表明，A1浅层中的抑制性中间神经元促进了听觉可塑性。 这些中间神经元的特征是表达5-羟色胺受体5HT3A-R，并对 乙酰胆碱。虽然多项研究都集中在乙酰胆碱信号在A1可塑性中的作用，但很少有研究 知道5-羟色胺的功能。这一建议侧重于浅层5HT3A-R中间神经元的子集 表达血管活性肠肽(VIP)，这是调节成人A1可塑性的一个有希望的靶点。 这些研究将检验5-羟色胺向血管活性肠肽中间神经元传递信号促进小鼠可塑性的假设。 A1在听觉知觉学习过程中。首先，将使用电路追踪技术来识别5-羟色胺- 在A1区表达与VIP中间神经元突触的神经元。第二，体内双光子成像将 确定在声音辨别过程中A1区5-羟色胺能终末和VIP中间神经元何时被招募 学习。这些研究将1)确定一个以前没有特征的5-羟色胺神经元到VIP中间神经元的回路， 以及2)将确定VIP中间神经元的5-羟色胺信号的变化是否是A1可塑性的基础 听觉知觉学习。这项研究的结果可能会为发现 利用特定的皮质回路来促进成人可塑性的新疗法。

Project Summary Auditory perceptual learning induces plasticity in the auditory cortex (A1) that can improve hearing perception, but the neural mechanisms that trigger these changes are unclear. Across sensory cortical regions, inhibitory interneurons are emerging as “gate keepers” to plasticity - regulating tightly controlled balances between excitation and inhibition. The cortical interneuron population is composed of numerous cell subtypes distinguished by morphology, physiology, and connectivity, suggesting that there are several distinct circuits for plasticity regulation. How these specific interneuron circuits contribute to cortical plasticity and sensory learning remains poorly understood. Recent work suggests that inhibitory interneurons within the superficial layers of A1 promote auditory plasticity. These interneurons are characterized by expression of the serotonin receptor, 5HT3A-R, and are responsive to acetylcholine. While multiple studies have focused on the role of acetylcholine signaling in A1 plasticity, little is known about the function of serotonin. This proposal focuses on a subset of superficial 5HT3A-R interneurons expressing vasoactive intestinal peptide (VIP) that are a promising target for regulating plasticity in adult A1. The studies will test the hypothesis that serotonin signaling to VIP interneurons promotes plasticity in mouse A1 during auditory perceptual learning. First, circuit tracing techniques will be used to identify the serotonin- expressing neurons that synapse onto VIP interneurons in A1. Second, in vivo two-photon imaging will determine when serotonergic terminals and VIP interneurons in A1 are recruited during sound discrimination learning. These studies will 1) identify a previously uncharacterized serotonin neuron to VIP interneuron circuit, and 2) will determine whether changes in serotonin signaling to VIP interneurons underlie A1 plasticity during auditory perceptual learning. The results of this research will likely open new horizons for the discovery of novel therapies that tap into specific cortical circuits to promote adult plasticity.