Global and compartmentalized serotonergic control of sensorimotor integration underlying motor adaptation

Haruvi, R.; Barbara, R.; Shainer, I.; Rosenberg, A. M.; Moshe, L.; Malamud, D.; Toledano, J.; Braun, D.; Baier, H.; Kawashima, T.

doi:10.1101/2024.09.15.613094

bioRxiv · 10.1101/2024.09.15.613094

Global and compartmentalized serotonergic control of sensorimotor integration underlying motor adaptation

Haruvi, R.·Barbara, R.·Shainer, I.·Rosenberg, A. M.·Moshe, L.·Malamud, D.·Toledano, J.·Braun, D.·Baier, H.·Kawashima, T.

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Abstract

The vertebrate serotonergic system plays a critical role in modulating adaptive behavior. Yet, it has been challenging to unravel the downstream targets and the effects of serotonin on ongoing neural dynamics due to its widespread innervation and the complex nature of receptor signaling. Here, we show that the serotonergic system controls brain-wide neural dynamics in a spatially dualistic manner, global and compartmentalized, during motor adaptation behavior in zebrafish. Larval zebrafish adapt the vigor of tail motions depending on environmental drag force during visual pursuit behavior in a serotonin-dependent manner. Whole-brain imaging of serotonin release and systematic spatial mapping of serotonin receptors showed highly compartmentalized patterns that span multiple brain areas. Interestingly, whole-brain neural activity imaging combined with the perturbation of tph2+ raphe serotonin neurons revealed dualistic modulation of neural activity depending on behavioral encoding: global suppression of locomotor networks and the compartmentalized enhancement of midbrain sensory networks, both of which synergistically enabled motor adaptation. The compartmentalized modulation resulted from local serotonin release and receptor expression, while the global effect was due to modulation of a key network hub that broadcasts behavioral state signals. Our results reveal how the serotonergic system interacts with brain-wide neural dynamics through its parallel interactions and provide a conceptual framework for understanding the neural mechanisms of widespread serotonergic behavioral control.

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Haruvi, R., Barbara, R., Shainer, I., Rosenberg, A. M., Moshe, L., Malamud, D., Toledano, J., Braun, D., Baier, H., Kawashima, T.. 2024-09-16. Global and compartmentalized serotonergic control of sensorimotor integration underlying motor adaptation. https://doi.org/10.1101/2024.09.15.613094

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