Synapse types are spatially associated with regional hemodynamics in the mouse brain

Hansen, Justine Y. and Luppi, Andrea I. and Qiu, Zhen and Gini, Silvia and Fulcher, Ben D. and Gozzi, Alessandro and Grant, Seth G. N. and Misic, Bratislav (2026) Synapse types are spatially associated with regional hemodynamics in the mouse brain. PLOS Biology, 24 (2). e3003637. ISSN 1545-7885 (https://doi.org/10.1371/journal.pbio.3003637)

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Abstract

Synapses are the connections that transform neurons from simple electrically charged cells into complex circuits that support perception, cognition and action. Recent advances in single-punctum synapse mapping in mice make studying synapse diversity and differential expression possible. How do diverse synapses relate to the spatial patterning of whole-brain dynamics? Here we map the spatial distribution of multiple synapse types to >6 000 time-series features from fMRI recordings in awake mice to understand the comprehensive dynamical phenotype of multiple synapse types. We find that specific synapse types are associated with specific features of haemodynamics, including high-amplitude events and signal stationarity. These variations in synapse types and dynamics are associated with the structural and functional network embedding of brain regions. Finally, using two additional fMRI datasets in anaesthetized mice, we show that synaptic protein lifetime reflects differential synaptic engagement across behavioural states. Collectively, this work suggests that the spatial organization of microscale synapse types may shape whole-brain dynamics.

ORCID iDs

Hansen, Justine Y., Luppi, Andrea I., Qiu, Zhen ORCID logoORCID: https://orcid.org/0000-0002-0226-7855, Gini, Silvia, Fulcher, Ben D., Gozzi, Alessandro, Grant, Seth G. N. and Misic, Bratislav;