A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex.
Andrea I. Luppi, Manesh Girn, Fernando E. Rosas, Christopher Timmermann, Leor Roseman, David Erritzøe, David Nutt, Emmanuel A. Stamatakis, R Nathan Spreng, Lei Xing, Wieland B Huttner, Robin Carhart-Harris
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Evolutionary expansion Uniquely human-expanded areas Transmodal cortex Sophisticated functioning High-level networks Functional integration Complexity Cognitive centers Serotonin receptor Neurodevelopment: development Evolutionary growth |
| Citations | 25 |
| Key findings | Serotonin 2A receptor signaling is both an evolutionary driver of human cortical expansion and a potent modulator of the transmodal cortex's integrative functions underlying complex cognition. |
Abstract
Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the cortex follows a unimodal-to-transmodal gradient. Situated at the apex of this processing hierarchy-where it plays a central role in the integrative processes underpinning complex, human-defining cognition-the transmodal cortex has disproportionately expanded across human development and evolution. Notably, the adult human transmodal cortex is especially rich in 5-HT2AR expression and recent evidence suggests that, during early brain development, 5-HT2AR signalling on neural progenitor cells stimulates their proliferation-a critical process for evolutionarily-relevant cortical expansion. Drawing on multimodal neuroimaging and cross-species investigations, we argue that, by contributing to the expansion of the human cortex and being prevalent at the apex of its hierarchy in the adult brain, 5-HT2AR signalling plays a major role in both human cortical expansion and functioning. Owing to its unique excitatory and downstream cellular effects, neuronal 5-HT2AR agonism promotes neuroplasticity, learning and cognitive and psychological flexibility in a context-(hyper)sensitive manner with therapeutic potential. Overall, we delineate a dual role of 5-HT2ARs in enabling both the expansion and modulation of the human transmodal cortex.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
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Cites 130
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- Default Mode Network Activity and Connectivity in Psychopathology Annual Review of Clinical Psychology March 29, 2012
and 125 more in the library