Transneuronal tracing of nociceptive circuits

伤害感受回路的跨神经元追踪

• 批准号: 8689190
• 负责人: Carlos Efrain Solorzano Say
• 金额: $ 3.53万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8689190
• 关键词: Address; Analgesics; Brain; Brain Stem; Cell Nucleus; Cells; Clinical; Detection; Development; Fiber; Fostering; Gene Expression; Genetic; Herpesvirus 1; Imagery; Incidence; Injury; Interneurons; Learning; Life Expectancy; Mechanics; Methods; Modality; Mus; Neurons; Nociception; Nociceptors; Organism; Pain; Pain management; Pathway interactions; Persistent pain; Population; Procedures; Process; Prosencephalon; Proteins; Recombinants; Reporter; Science; Signal Transduction; Spinal; Spinal Cord; Stimulus; Substance P; Substance P Receptor; Synapses; TRPV1 gene; Techniques; Testing; Tissues; Tracer; Training; Transgenic Mice; Virus; Wheat Germ Agglutinins; cellular targeting; dorsal horn; heat stimulus; innovation; magnocellular; novel; raphe nucleus magnus; recombinase; research study; response

DESCRIPTION (provided by applicant): The long-term objective of the studies outlined in this proposal is to investigate whether different pain modalities are conveyed to the brain via distinct neuronal circuits and to elucidate the mechanisms by which these signals are regulated under normal conditions and in the setting of injury-induced persistent pain. There is evidence for specialization of primary afferent 'pain' fibers for the detection of different noxious stimulus modalities but whether modality-specific afferents engage separate spinal and supraspinal cord circuits, is unclear. Experiments proposed in this application will investigate the neuronal circuis engaged by the TRPV1- expressing population of primary afferents, which is critical for the detection of thermal (heat) stimuli, and the MrgprD-expressing primary afferents, which have been implicated in the response to mechanical stimuli. In related experiments we will investigate the neuronal circuits engaged by descending brainstem serotonergic neurons, which modulate the processing of ascending 'pain' signals at the level of the spinal cord. These tract- tracing studies will be performed using an innovative approach in which anterograde transneuronal transfer of a virus can be triggered in defined subsets of neurons, using expression of the Cre recombinase to induce the virus. This novel tracing method will allow for the sensitive visualization of neuronal circuits engaged by distinct 'nociresponsive' cells and the serotonergic regulatory neurons of the brainstem. Results from these studies will contribute to the development of novel/more effective pain therapies targeted at the neuronal populations and circuits responsible for transmitting distinct modalities of pain.

描述（由申请人提供）：该提案中概述的研究的长期目标是研究是否通过不同的疼痛方式传达给大脑 神经元电路并阐明在正常条件下和受伤引起的持续性疼痛的情况下调节这些信号的机制。有证据表明，主要传入的“疼痛”纤维用于检测不同的有害刺激方式，但是特定于模态特异性的传入是否参与单独的脊柱和脊髓索上循环。本应用中提出的实验将研究TRPV1-表达的主要传入群体所参与的神经元马基，这对于检测热（热）刺激和表达MRGPRD的主要传入至关重要，这与机械刺激的反应有关。在相关的实验中，我们将研究降低的脑干血清素能神经元参与的神经元电路，该神经元调节脊髓水平上升上“疼痛”信号的处理。这些拖拉研究将使用创新的方法进行，在这种方法中，可以在神经元的定义的神经元中触发病毒的顺行跨神经元转移，并使用CRE重组酶的表达来诱导病毒。这种新颖的追踪方法将允许通过独特的“非副措施”细胞和脑干的血清素能调节神经元参与的神经元电路的敏感可视化。这些研究的结果将有助于发展针对神经元种群的新型/更有效的疼痛疗法，并导致负责传播不同疼痛方式的电路。