Fine Structure of Lamina I TSST Terminals in VP

VP 中 Lamina I TSST 端子的精细结构

• 批准号: 6680136
• 负责人: ARTHUR D CRAIG
• 金额: $ 14.99万
• 依托单位: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6680136
• 关键词: Macaca fascicularis; brain mapping; brain morphology; central neural pathway /tract; computational neuroscience; histology; intercellular connection; neural information processing; pain; physical model; sensory mechanism; subthalamus; synapses; thalamic nuclei

DESCRIPTION (provided by applicant): In order to understand the organization of central pathways for pain in humans, we need to know the underlying anatomical substrates in the primate brain. During the past several years, we have characterized a thalamic nucleus in monkeys and humans (VMpo) that, we believe, serves as a specific thalamocortical relay nucleus for pain, temperature, itch and other sensations related to the physiological condition of the body. This hypothesis differs from the conventional view that the ventral posterior nuclei (VP) are crucial for pain sensation, but it is supported by growing evidence. The preceding cycle of this NIH grant enabled us to test this hypothesis by examining the synaptology of lamina I trigemino- and spino-thalamic (TSTT) terminations in VMpo. Using three-dimensional models built from serial ultra-thin sections through anterogradely-labeled lamina I TSTT terminal fibers, we showed that lamina I terminations in VMpo have distinct characteristics (multiple contacts on single post-synaptic dendrites in triadic arrangements with presynaptic dendrites) that provide the basis for secure, high-fidelity synaptic transmission, consistent with a relay function. This contrasts strongly with prior ultrastructural observations by reliable investigators indicating that TSTT terminals in the primate thalamus generate single, isolated boutons that do not provide the basis for secure, high-fidelity synaptic contacts. That prior study focused on VP, but it also examined the region of VMpo; yet, it did not differentiate lamina I from lamina V TSTT terminations, which may have entirely different functional roles. We propose to resolve this discrepancy by directly examining the synaptology of identified lamina I TSTT terminations in VP. If lamina I TSTT terminations in VP form secure, high-fidelity synaptic contacts like they do in VMpo, this would support the view that both these regions have an important role in pain. Alternatively, if lamina I TSTT terminations in VP form single contacts, as suggested by prior observations, this would indicate that the synaptic transfer of pain-related activity in VMpo and VP is qualitatively different, supporting our view that VMpo and VP have different roles in sensation, and underscoring the significance of VMpo as a lamina I sensory relay nucleus. These studies will advance our understanding of the anatomical substrates for pain sensation in the primate thalamus.

描述（由申请人提供）：为了了解人类疼痛中枢通路的组织，我们需要知道灵长类动物大脑的潜在解剖学基础。在过去的几年里，我们已经对猴子和人类的丘脑核（VMpo）进行了表征，我们认为它是一个特定的丘脑皮质中继核，负责疼痛、温度、瘙痒和其他与身体生理状况相关的感觉。这一假设不同于传统的观点，即腹侧后核（VP）是痛觉的关键，但越来越多的证据支持它。NIH拨款的前一个周期使我们能够通过检查VMpo中三叉神经和脊髓丘脑（TSTT）末端的I层突触学来验证这一假设。通过顺行标记的I层TSTT末端纤维的连续超薄切片建立三维模型，我们发现VMpo的I层末端具有明显的特征（单个突触后树突上的多个接触与突触前树突呈三联排列），这为安全、高保真的突触传输提供了基础，符合中继功能。这与先前可靠的研究人员的超微结构观察结果形成强烈对比，后者表明灵长类丘脑的TSTT终端产生单个、孤立的钮扣，这些钮扣不能提供安全、高保真的突触接触的基础。先前的研究主要关注VP，但也研究了VMpo区域；然而，它不能区分TSTT的I层和V层终止，这两种终止可能具有完全不同的功能作用。我们建议通过直接检查VP中已识别的I层TSTT末端的突触学来解决这一差异。如果第1层TSTT终止在VP中形成安全、高保真的突触接触，就像在VMpo中一样，这将支持这两个区域在疼痛中起重要作用的观点。或者，如果像之前观察的那样，VMpo和VP中疼痛相关活动的突触传递在性质上是不同的，这支持了我们的观点，即VMpo和VP在感觉中具有不同的作用，并强调了VMpo作为I层感觉传递核的重要性。这些研究将促进我们对灵长类丘脑疼痛感觉的解剖学基础的理解。