Department of Neurobiology, University of Chicago, Chicago, IL 60637.
Proc Natl Acad Sci U S A. 2022 May 24;119(21):e2201481119. doi: 10.1073/pnas.2201481119. Epub 2022 May 19.
Higher-order thalamic nuclei contribute to sensory processing via projections to primary and higher cerebral cortical areas, but it is unknown which of their cortical and subcortical inputs contribute to their distinct output pathways. We used subpopulation specific viral strategies in mice to anatomically and physiologically dissect pathways of the higher-order thalamic nuclei of the somatosensory and visual systems (the posterior medial nucleus and pulvinar). Employing a complementary optogenetics and electrical stimulation strategy, we show that synapses in cortex from higher-order thalamus have functionally divergent properties in primary vs. higher cortical areas. Higher-order thalamic projections onto excitatory targets in S1 and V1 were weakly modulatory, while projections to S2 and higher visual areas were strong drivers of postsynaptic targets. Then, using transsynaptic tracing verified by optogenetics to map inputs to higher-order thalamus, we show that posterior medial nucleus cells projecting to S1 are driven by neurons in layer 5 of S1, S2, and M1 and that pulvinar cells projecting to V1 are driven by neurons in layer 5 of V1 and higher visual areas. Therefore, in both systems, layer 5 of primary and higher cortical areas drives transthalamic feedback modulation of primary sensory cortex through higher-order thalamus. These results highlight conserved organization that may be shared by other thalamocortical circuitry. They also support the hypothesis that direct corticocortical projections in the brain are paralleled by transthalamic pathways, even in the feedback direction, with feedforward transthalamic pathways acting as drivers, while feedback through thalamus is modulatory.
高级丘脑核通过向初级和高级大脑皮层区域的投射参与感觉处理，但尚不清楚它们的皮层和皮层下输入中的哪些有助于它们独特的输出途径。我们使用小鼠中特定于亚群的病毒策略，从解剖学和生理学上剖析了感觉系统（后内侧核和丘脑枕）和视觉系统的高级丘脑核的通路。采用互补的光遗传学和电刺激策略，我们表明来自高级丘脑的皮质中的突触在初级和高级皮质区域中具有功能上不同的特性。高级丘脑投射到 S1 和 V1 中的兴奋性靶标是弱调节性的，而投射到 S2 和更高的视觉区域是突触后靶标的强驱动因素。然后，我们使用经光遗传学验证的转导追踪来映射到高级丘脑的输入，表明投射到 S1 的后内侧核细胞由 S1、S2 和 M1 的第 5 层神经元驱动，而投射到 V1 的丘脑枕细胞由 V1 和更高的视觉区域的第 5 层神经元驱动。因此，在这两个系统中，初级和高级皮质区域的第 5 层通过高级丘脑驱动对初级感觉皮层的丘脑反馈调制。这些结果突出了保守的组织，可能由其他丘脑皮质回路共享。它们还支持这样的假设，即在大脑中直接的皮质-皮质投射与丘脑内的转导途径平行，即使在反馈方向上也是如此，前馈转导丘脑途径作为驱动因素，而通过丘脑的反馈是调节性的。
