Fine Structure of Lamina I TSST Terminals in VP

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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.