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Vertebrate brains have a dual structure, composed of ( i ) axons that can be well-captured with graph-theoretical methods and ( ii ) axons that form a dense matrix in which neurons with precise connections operate. A core part of this matrix is formed by axons (fibers) that store and release 5-hydroxytryptamine (5-HT, serotonin), an ancient neurotransmitter that supports neuroplasticity and has profound implications for mental health. The self-organization of the serotonergic matrix is not well understood, despite recent advances in experimental and theoretical approaches. In particular, individual serotonergic axons produce highly stochastic trajectories, fundamental to the construction of regional fiber densities, but further advances in predictive computer simulations require more accurate experimental information. This study examined single serotonergic axons in culture systems (co-cultures and monolayers), by using a set of complementary high-resolution methods: confocal microscopy, holotomography (refractive index-based live imaging), and super-resolution (STED) microscopy. It shows that serotonergic axon walks in neural tissue may strongly reflect the stochastic geometry of this tissue and it also provides new insights into the morphology and branching properties of serotonergic axons. The proposed experimental platform can support next-generation analyses of the serotonergic matrix, including seamless integration with supercomputing approaches.
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5‐HT1A regulates axon outgrowth in a subpopulation of Drosophila serotonergic neurons
Abstract Serotonergic neurons produce extensively branched axons that fill most of the central nervous system, where they modulate a wide variety of behaviors. Many behavioral disorders have been correlated with defective serotonergic axon morphologies. Proper behavioral output therefore depends on the precise outgrowth and targeting of serotonergic axons during development. To direct outgrowth, serotonergic neurons utilize serotonin as a signaling molecule prior to it assuming its neurotransmitter role. This process, termed serotonin autoregulation, regulates axon outgrowth, branching, and varicosity development of serotonergic neurons. However, the receptor that mediates serotonin autoregulation is unknown. Here we asked if serotonin receptor 5‐HT1A plays a role in serotonergic axon outgrowth and branching. Using culturedDrosophilaserotonergic neurons, we found that exogenous serotonin reduced axon length and branching only in those expressing 5‐HT1A. Pharmacological activation of 5‐HT1A led to reduced axon length and branching, whereas the disruption of 5‐HT1A rescued outgrowth in the presence of exogenous serotonin. Altogether this suggests that 5‐HT1A is a serotonin autoreceptor in a subpopulation of serotonergic neurons and initiates signaling pathways that regulate axon outgrowth and branching duringDrosophiladevelopment.
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- Award ID(s):
- 2232510
- PAR ID:
- 10463113
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Developmental Neurobiology
- Volume:
- 83
- Issue:
- 7-8
- ISSN:
- 1932-8451
- Format(s):
- Medium: X Size: p. 268-281
- Size(s):
- p. 268-281
- Sponsoring Org:
- National Science Foundation
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