Fine Structure of Lamina I TSST Terminals in VP

描述(申请人提供)：为了了解人类疼痛的中枢通路的组织，我们需要知道灵长类动物大脑的基本解剖学基础。在过去的几年里，我们已经确定了猴子和人类的丘脑核(VMPO)的特征，我们认为它是一个特定的丘脑皮质中继核，负责与身体生理状况有关的疼痛、温度、瘙痒和其他感觉。这一假说不同于传统的观点，即腹侧后核(VP)对痛觉至关重要，但越来越多的证据支持这一假说。这项NIH拨款的前一个周期使我们能够通过检查VMpo内I层三叉神经和棘丘脑(TSTT)终末的突触学来检验这一假说。利用连续超薄切片通过顺行标记的板层I TSTT终末纤维建立的三维模型，我们发现VMPO的板层I终末具有明显的特征(单个突触后树突上的多个接触与突触前树突形成三分排列)，这些特征为安全、高保真的突触传递提供了基础，与中继功能一致。这与可靠的研究人员先前的超微结构观察形成了强烈的对比，这些超微结构观察表明，灵长类丘脑中的TSTT终末产生单一的、孤立的突触，而这些突触不能为安全、高保真的突触接触提供基础。先前的研究侧重于VP，但也研究了VMPO的区域；然而，它没有区分I层和V层TSTT终末，后者可能具有完全不同的功能作用。我们建议通过直接检查Vp内已发现的I型TSTT终末的突触来解决这一差异。如果Vp内的I型TSTT终末形成安全、高保真的突触接触，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Vp内的I型TSTT终末形成单一接触，这将表明VMPO和Vp内痛相关活动的突触传递在性质上是不同的，支持我们的观点，即VMPO和Vp在感觉中具有不同的角色，并强调了VMPO作为I型感觉中继核的重要性。这些研究将促进我们对灵长类丘脑痛觉的解剖学基础的理解。

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.