Abstract
During the last 50 years, the serotonergic (5-HT) system was reported to exert a complex modulation of locomotor activity. Here, we focus on two key factors that likely contribute to such complexity. First, locomotion is modulated directly and indirectly by 5-HT neurons. The locomotor circuitry is directly innervated by 5-HT neurons in the caudal brainstem and spinal cord. Also, indirect control of locomotor activity results from ascending projections of 5-HT cells in the rostral brainstem that innervate multiple brain centers involved in motor action planning. Second, each approach used to manipulate the 5-HT system likely engages different 5-HT-dependent mechanisms. This includes the recruitment of different 5-HT receptors, which can have excitatory or inhibitory effects on cell activity. These receptors can be located far or close to the 5-HT release sites, making their activation dependent on the level of 5-HT released. Here we review the activity of different 5-HT nuclei during locomotor activity, and the locomotor effects of 5-HT precursors, exogenous 5-HT, selective 5-HT reuptake inhibitors (SSRI), electrical or chemical stimulation of 5-HT neurons, genetic deletions, optogenetic and chemogenetic manipulations. We highlight both the coherent and controversial aspects of 5-HT modulation of locomotor activity from basal vertebrates to mammals. This mini review may hopefully inspire future studies aiming at dissecting the complex effects of 5-HT on locomotor function.
Highlights
The role of the serotonergic (5-HT) system is well known to be an enigma (Jacobs and Fornal, 1995). 5-HT modulates animal cognition and behavior, including motor function, in a complex manner
The activity of genetically identified 5-HT neurons was reported using in vivo calcium imaging, and their activity during ongoing locomotion was manipulated with optogenetics and chemogenetics
Because genetic tools are mostly available in rodents and zebrafish, the present section as well as the three following ones focus essentially on studies in these animal models. 5-HT neurons can be targeted for specific genetic deletions. 5-HT neurons express molecular markers such as the 5-HT transporter (SERT) gene, the erythroblast transformation-specific domain (Pet1) gene or the Tryptophan hydroxylase 2 (Tph2) gene, an enzyme involved in the synthesis of 5-HT
Summary
Aurélie Flaive 1, Maxime Fougère 1, Cornelis Immanuel van der Zouwen 1 and Dimitri Ryczko 1,2,3,4*. Each approach used to manipulate the 5-HT system likely engages different 5-HT-dependent mechanisms This includes the recruitment of different 5-HT receptors, which can have excitatory or inhibitory effects on cell activity. We review the activity of different 5-HT nuclei during locomotor activity, and the locomotor effects of 5-HT precursors, exogenous 5-HT, selective 5-HT reuptake inhibitors (SSRI), electrical or chemical stimulation of 5-HT neurons, genetic deletions, optogenetic and chemogenetic manipulations. We highlight both the coherent and controversial aspects of 5-HT modulation of locomotor activity from basal vertebrates to mammals. This mini review may hopefully inspire future studies aiming at dissecting the complex effects of 5-HT on locomotor function
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