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Abstract Persistent delay-period activity in prefrontal cortex (PFC) has long been regarded as a neural signature of working memory (WM). Electrophysiological investigations in macaque PFC have provided much insight into WM mechanisms; however, a barrier to understanding is the fact that a portion of PFC lies buried within the principal sulcus in this species and is inaccessible for laminar electrophysiology or optical imaging. The relatively lissencephalic cortex of the New World common marmoset (Callithrix jacchus) circumvents such limitations. It remains unknown, however, whether marmoset PFC neurons exhibit persistent activity. Here, we addressed this gap by conducting wireless electrophysiological recordings in PFC of marmosets performing a delayed-match-to-location task on a home cage-based touchscreen system. As in macaques, marmoset PFC neurons exhibited sample-, delay-, and response-related activity that was directionally tuned and linked to correct task performance. Models constructed from population activity consistently and accurately predicted stimulus location throughout the delay period, supporting a framework of delay activity in which mnemonic representations are relatively stable in time. Taken together, our findings support the existence of common neural mechanisms underlying WM performance in PFC of macaques and marmosets and thus validate the marmoset as a suitable model animal for investigating the microcircuitry underlying WM.
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This content will become publicly available on March 17, 2026
From comparative connectomics to large-scale working memory modeling in macaque and marmoset
Abstract Although macaques and marmosets are both primates of choice for studying the brain mechanisms of cognition, they differ in key aspects of anatomy and behavior. Interestingly, recent connectomic analysis revealed that strong top-down projections from the prefrontal cortex to the posterior parietal cortex, present in macaques and important for executive function, are absent in marmosets. Here, we propose a consensus mapping that bridges the two species’ cortical atlases and allows for direct area-to-area comparison of their connectomes, which are then used to build comparative computational large-scale modeling of the frontoparietal circuit for working memory. We found that the macaque model exhibits resilience against distractors, a prerequisite for normal working memory function. By contrast, the marmoset model is sensitive to distractibility commonly observed behaviorally in this species. Surprisingly, this contrasting trend can be swapped by scaling intrafrontal and frontoparietal connections. Finally, the relevance to primate ethology and evolution is discussed. Graphical Abstract HighlightsConsensus mapping allows for directly comparing macaque and marmoset connectomes.Connectomes and spine counts constrain large-scale models of working memory.The marmoset model is susceptible to distraction, but not the macaque.Our results capture real life difference with regard to distraction.
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- Award ID(s):
- 2015276
- PAR ID:
- 10616347
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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