Mapping brain-wide excitatory projectome of primate prefrontal cortex at submicron resolution and comparison with diffusion tractography

Abstract

Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here, we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic, and subcortical areas, relatively weak projections to parietal and insular regions but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative green fluorescent protein-labeled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.

The spatial extent of anatomical connections within the thalamus varies across the cortical hierarchy in humans and macaques

“…Such cross-species dMRI analyses provide a bridge with the extensive tract tracing literature in non-human primates. The integration of macaque tractography and tracer data in cortico-thalamic systems remains limited (79, 80), but future studies incorporating tracer data could provide more specific insights into cortico-thalamic system organization by considering directionality, as feed-forward and feed-back thalamic connections vary across cortical areas and may provide more specific insights into the functional roles of these circuits. On the other hand, dMRI-derived tractography data can address gaps in the non-human primate tracer literature.…”

Travelling waves or sequentially activated discrete modules: mapping the granularity of cortical propagation

“…Similarly, sequentially activating adjacent cortical regions, which are functionally correlated and structurally connected (e.g., as activity travels across visual regions from V1 to V4), may be activated in a modular fashion but identified as travelling in VSD signals (Gu et al, 2021) due to mesoscale connectivity (Oh et al, 2014; Yan et al, 2022). Such modularity would be harder to detect for fast waves (in contrast to the slow waves in turtle cortex).…”

Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

“…The primate (vervet monkey) brain exhibits similar architecture to the human brain, which makes it highly suitable for neuroscientific studies [45] of structure [46] and function [47]. Besides, most knowledge of gold-standard human connectivity comes from tracer studies in primates [8], [48], [49]. 3D-Polarized Light Imaging of vervet monkey brain regions has provided micrometer resolution fiber orientations maps [46], while scattered light imaging has additionally enabled discerning crossing nerve fibers [18], [29], [31].…”