Chinese Academy of Sciences Maps Macaque Brain Connectivity for Cognitive Function Insights

Researchers from the Chinese Academy of Sciences and the HUST-Suzhou Institute for Brainsmatics have mapped 2,231 single-neuron projectomes within the macaque prefrontal cortex, classifying them into 32 subtypes distinguished by axonal morphology and targeting specific brain regions including the parietal and temporal cortices. Utilizing a new high-throughput system called Gapr, the team demonstrated that macaque PFC neurons exhibit simpler structures and more restricted projection targets compared to those in mice, suggesting a more spatially refined innervation pattern potentially underpinning advanced cognitive functions. The study also revealed distinct organizational principles within the macaque PFC, including a modular network of intra-PFC connections and a preference for contralateral targeting in neurons projecting to the opposite hemisphere.

Macaque Prefrontal Cortex Connectivity Mapped at Single-Neuron Level

Researchers have, for the first time, conducted a comprehensive study of whole-brain projectomes in the macaque prefrontal cortex (PFC) at the single-neuron level, yielding 2,231 single-neuron projectomes of the macaque PFC obtained through viral injection and fluorescence micro-optical sectioning tomography (fMOST) imaging. These neurons were classified into 32 projection subtypes based on axonal morphology throughout the whole brain, each exhibiting distinct projection patterns targeting various brain regions including the parietal and temporal cortices, contralateral hemisphere, striatum, thalamus, midbrain, and pons. AI-based functional predictions suggest these subtypes are closely associated with sensory, motor, emotional, cognitive, and memory-related biological functions.

In-depth analysis of the macaque PFC revealed distinct neuron subtypes projecting to either the parietal or temporal lobes, and neurons in different PFC subregions projecting to different subregions within these target areas. The macaque PFC exhibits a modular network of intra-PFC connections, potentially providing a structural basis for working memory, and patchy terminal arbors were found in PFC projections to the striatum and contralateral cortex. Macaque PFC neurons with bilateral projections show a stronger preference for contralateral targeting compared to those in mice, suggesting functional specialization of neurons projecting to the contralateral hemisphere in primates.

Through systematic comparison between macaque and mouse PFC single-neuron projectomes, researchers found that macaque PFC neurons share similar target specificity but exhibit distinct morphological features, including longer axon trunks, fewer collateral branches, and relatively smaller axon terminal arbors. These findings demonstrate that, compared to rodent neurons, primate neurons possess simpler structures, more restricted projection targets, and a more spatially refined innervation pattern, suggesting this highly modular and selective connectivity of the primate PFC may provide the structural foundation for the emergence of advanced cognitive and executive functions in primate brains, and contributes to understanding primate brain connectivity.

Primate PFC Organisation and Evolutionary Distinctiveness

PFC neurons projecting to subcortical areas display a topographic relationship between their somata and targets, suggesting differential downstream innervations across different prefrontal regions. This detailed mapping of connections contributes to a greater understanding of primate brain connectivity and its functional implications.

Researchers developed the Fast Neurite Tracer (FNT), evolving it into Gapr, a high-throughput system integrating petabyte-scale data processing, AI-algorithm-based automatic reconstruction, and large-scale collaborative proofreading, to facilitate the mapping of single-neuron projectomes in primate brains. The development of this technology was crucial for managing the extremely large datasets generated by capturing whole-brain images tracing individual axons in the primate brain.

Compared to mice, macaques exhibit patchy terminal arbors in PFC projections to the striatum and contralateral cortex, highlighting a more spatially refined innervation pattern in the primate brain. Furthermore, macaque PFC neurons share similar target specificity with those of mice, but demonstrate distinct morphological features, including longer axon trunks, fewer collateral branches, and relatively smaller axon terminal arbors. These morphological differences, alongside the refined innervation patterns, suggest a unique organization of primate brain connectivity.

Implications for Neuroscience and Artificial Intelligence

PFC neurons projecting to subcortical areas display a topographic relationship between their somata and targets, suggesting differential downstream innervations across different prefrontal regions. This organization is consistent with the detailed mapping of single-neuron projectomes achieved in this study, contributing to an understanding of primate brain connectivity and its functional implications.

Systematic comparison between macaque and mouse PFC single-neuron projectomes revealed that macaque PFC neurons share similar target specificity but exhibit distinct morphological features, including longer axon trunks, fewer collateral branches, and relatively smaller axon terminal arbors. These findings demonstrate that, compared to rodent neurons, primate neurons possess simpler structures, more restricted projection targets, and a more spatially refined innervation pattern, suggesting a unique organization of primate brain connectivity.

The macaque PFC exhibits a modular network of intra-PFC connections, potentially providing a structural basis for working memory, and patchy terminal arbors were found in PFC projections to the striatum and contralateral cortex. These findings highlight a more spatially refined innervation pattern in the primate brain, differing from that observed in mice, and contributing to understanding primate brain connectivity.

Researchers developed the Fast Neurite Tracer (FNT), evolving it into Gapr, a high-throughput system integrating petabyte-scale data processing, AI-algorithm-based automatic reconstruction, and large-scale collaborative proofreading, to facilitate the mapping of single-neuron projectomes in primate brains. This technological advancement was crucial for managing the extremely large datasets generated by capturing whole-brain images tracing individual axons in the primate brain, enabling detailed analysis of primate brain connectivity.