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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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This content will become publicly available on July 17, 2026
Spinally Projecting Serotonergic Neurons in Motor Network Modulation
Spinally projecting serotonergic (5-HTsp) neurons represent a heterogeneous population of neurons in the brainstem whose relevance in the control of movement has largely been inferred. Numerous studies across a variety of species have suggested that 5-HTsp neurons exert a widespread influence on spinal sensorimotor networks, operating at multiple levels (primary afferents, interneurons, and motoneurons) through various serotonin receptor subtypes. However, despite the anatomical and neurochemical complexity of the 5-HTsp system, most supporting evidence has largely been derived from indirect approaches (e.g., exogenous application of 5-HT and agonists/antagonists of 5-HT receptors). Direct demonstrations of specific anatomical and functional connectivity have been limited, occasionally yielding apparent discrepant results. Consequently, as the primary provider of serotonin to the spinal cord, the exact contributions of the 5-HTsp neurons remain to be fully elucidated. For this mini-review, we sifted through the literature of the last six decades, starting after the characterization of the brainstem raphe nuclei and monoaminergic systems [1–3], to provide a clearer picture of what is currently known of the anatomy and influences of the different populations of 5-HTsp neurons on sensorimotor circuits and motor behaviors. We focused on studies reporting direct manipulation of brainstem 5-HTsp neurons, excluding those targeting 5-HT neurotransmission by exogenous application of 5-HT. This emphasis aims to highlight the urgency of resolving how 5-HTsp neuron subpopulations differentiate anatomically and functionally, so that they can be integrated as dedicated components in current models of supraspinal control of movement and motor diseases such as Parkinson‘s and amyotrophic lateral sclerosis. Along the way, we point out gaps in knowledge that may be filled using newly available research tools.
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- Award ID(s):
- 2015317
- PAR ID:
- 10627483
- Publisher / Repository:
- American Physiological Society
- Date Published:
- Journal Name:
- Journal of Neurophysiology
- ISSN:
- 0022-3077
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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