Serotonin functions as a bidirectional guidance molecule regulating growth cone motility.
Animals
Axon Guidance
/ drug effects
Axons
/ drug effects
Calcium
/ metabolism
Cell Movement
/ drug effects
Cells, Cultured
Female
Growth Cones
/ drug effects
Humans
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1B
Receptors, Serotonin, 5-HT2
Sensory Receptor Cells
/ cytology
Serotonin
/ pharmacology
Axon guidance
Axon pathfinding
Circuit development
Growth cone
Guidance cue
Serotonin
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
29
06
2020
accepted:
21
08
2020
revised:
14
08
2020
pubmed:
18
9
2020
medline:
30
3
2021
entrez:
17
9
2020
Statut:
ppublish
Résumé
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 µM serotonin elicited attraction, mediated by the serotonin 5-HT2a receptor while 100 µM 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.
Identifiants
pubmed: 32939562
doi: 10.1007/s00018-020-03628-2
pii: 10.1007/s00018-020-03628-2
doi:
Substances chimiques
Receptor, Serotonin, 5-HT1B
0
Receptors, Serotonin, 5-HT2
0
Serotonin
333DO1RDJY
Calcium
SY7Q814VUP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2247-2262Références
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