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Serotonin functions as a bidirectional guidance molecule regulating growth cone motility


Vicenzi, S and Foa, L and Gasperini, RJ, Serotonin functions as a bidirectional guidance molecule regulating growth cone motility, Cellular and Molecular Life Sciences, 78, (5) pp. 2247-2262. ISSN 1420-9071 (2020) [Refereed Article]


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Springer Nature Switzerland AG 2020. The final publication is available at:

DOI: doi:10.1007/s00018-020-03628-2


The neurotransmitter serotonin has been implicated in a range of complex neurological disorders linked to alterations of neuronal circuitry. Serotonin is synthesized in the developing brain before most neuronal circuits become fully functional, suggesting that serotonin might play a distinct regulatory role in shaping circuits prior to its function as a classical neurotransmitter. In this study, we asked if serotonin acts as a guidance cue by examining how serotonin alters growth cone motility of rodent sensory neurons in vitro. Using a growth cone motility assay, we found that serotonin acted as both an attractive and repulsive guidance cue through a narrow concentration range. Extracellular gradients of 50 然 serotonin elicited attraction, mediated by the serotonin 5-HT2a receptor while 100 然 serotonin elicited repulsion mediated by the 5-HT1b receptor. Importantly, high resolution imaging of growth cones indicated that these receptors signalled through their canonical pathways of endoplasmic reticulum-mediated calcium release and cAMP depletion, respectively. This novel characterisation of growth cone motility in response to serotonin gradients provides compelling evidence that secreted serotonin acts at the molecular level as an axon guidance cue to shape neuronal circuit formation during development.

Item Details

Item Type:Refereed Article
Keywords:serotonin, growth cone, axon guidance, guidance cue, circuit development, axon pathfnding
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Vicenzi, S (Miss Silvia Vicenzi)
UTAS Author:Foa, L (Professor Lisa Foa)
UTAS Author:Gasperini, RJ (Dr Rob Gasperini)
ID Code:141015
Year Published:2020
Web of Science® Times Cited:3
Deposited By:Medicine
Deposited On:2020-09-18
Last Modified:2022-08-23
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