Cassidy Rachel M, Macias Angel V, Lagos Willian N, Ugorji Chiamaka, Callaway Edward M
The Salk Institute for Biological Studies, La Jolla, California 92037.
Neurosciences Graduate Program, University of California, San Diego, La Jolla, California 92037.
J Neurosci. 2025 Jan 29;45(5):e1167242024. doi: 10.1523/JNEUROSCI.1167-24.2024.
Corticocortical (CC) projections in the visual system facilitate hierarchical processing of sensory information. In addition to direct CC connections, indirect cortico-thalamo-cortical (CTC) pathways through the pulvinar nucleus of the thalamus can relay sensory signals and mediate cortical interactions according to behavioral demands. While the pulvinar connects extensively to the entire visual cortex, it is unknown whether transthalamic pathways link all cortical areas or whether they follow systematic organizational rules. Because mouse pulvinar neurons projecting to different areas are spatially intermingled, their input/output relationships have been difficult to characterize using traditional anatomical methods. To determine the organization of CTC circuits, we mapped the higher visual areas (HVAs) of male and female mice with intrinsic signal imaging and targeted five pulvinar→HVA pathways for projection-specific rabies tracing. We aligned postmortem cortical tissue to in vivo maps for precise quantification of the areas and cell types projecting to each pulvinar→HVA population. Layer 5 corticothalamic (L5CT) "driver" inputs to the pulvinar originate predominantly from primary visual cortex (V1), consistent with the CC hierarchy. L5CT inputs from lateral HVAs specifically avoid driving reciprocal connections, consistent with the "no-strong-loops" hypothesis. Conversely, layer 6 corticothalamic (L6CT) "modulator" inputs are distributed across areas and are biased toward reciprocal connections. Unlike previous studies in primates, we find that every HVA receives disynaptic input from the superior colliculus. CTC circuits in the pulvinar thus depend on both target HVA and input cell type, such that driving and modulating higher-order pathways follow complementary connection rules similar to those governing first-order CT circuits.
视觉系统中的皮质-皮质（CC）投射促进了感觉信息的分层处理。除了直接的CC连接外，通过丘脑枕核的间接皮质-丘脑-皮质（CTC）通路可以中继感觉信号，并根据行为需求介导皮质间的相互作用。虽然丘脑枕与整个视觉皮质广泛连接，但尚不清楚经丘脑通路是否连接所有皮质区域，或者它们是否遵循系统的组织规则。由于投射到不同区域的小鼠丘脑枕神经元在空间上相互交织，使用传统解剖学方法很难表征它们的输入/输出关系。为了确定CTC回路的组织方式，我们用内在信号成像绘制了雄性和雌性小鼠的高级视觉区域（HVA），并针对五条丘脑枕→HVA通路进行了投射特异性狂犬病追踪。我们将死后的皮质组织与体内图谱对齐，以精确量化投射到每个丘脑枕→HVA群体的区域和细胞类型。向丘脑枕的第5层皮质丘脑（L5CT）“驱动”输入主要来自初级视觉皮质（V1），这与CC层次结构一致。来自外侧HVA的L5CT输入特别避免驱动相互连接，这与“无强环”假说一致。相反，第6层皮质丘脑（L6CT）“调制”输入分布在各个区域，并且倾向于相互连接。与之前对灵长类动物的研究不同，我们发现每个HVA都接受来自上丘的双突触输入。因此，丘脑枕中的CTC回路既取决于目标HVA，也取决于输入细胞类型，使得驱动和调制高阶通路遵循与控制一阶CT回路相似的互补连接规则。
