Serotonergic influences on locomotor circuits

Sławińska, Urszula; Jordan, Larry M.

doi:10.1016/j.cophys.2018.12.012

Cited by 16 publications

(6 citation statements)

References 76 publications

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“…We highlight the controversies and the possible future developments. Other important aspects of 5-HT modulation include its role during spinal network development (for review Jean-Xavier et al, 2018 ; Hachoumi and Sillar, 2020 ), the specific contributions of the different 5-HT receptor subtypes and the plasticity of 5-HT modulation after spinal cord injury (for review Sławińska et al, 2014b ; Ghosh and Pearse, 2015 ; Perrier and Cotel, 2015 ; Perrin and Noristani, 2019 ; Sławińska and Jordan, 2019 ). For further reading on the role of 5-HT in spinal cord-transected animal models and complete spinal cord-injured patients, we refer readers to the studies of the laboratories of e.g., Courtine, Edgerton, Guertin, Jordan, Orsal, or Slawinska.…”

Section: Introductionmentioning

confidence: 99%

Serotonergic Modulation of Locomotor Activity From Basal Vertebrates to Mammals

Flaive

Fougère

Zouwen

et al. 2020

Front. Neural Circuits

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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.

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Section: Introductionmentioning

confidence: 99%

Serotonergic Modulation of Locomotor Activity From Basal Vertebrates to Mammals

Flaive

Fougère

Zouwen

et al. 2020

Front. Neural Circuits

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“…It is well recognized that 5-HT also regulates locomotion and motor behavior [ 54 , 132 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 ]. For reviews, see [ 159 , 160 ]. For motor control, 5-HT pathways originate from the B1 and B2 regions of the medulla and project to the motoneurons and interneurons in laminae VII and VIII of the spinal cord [ 118 , 161 , 162 , 163 ].…”

Section: Serotonin Function In the Uninjured Nervous Systemmentioning

confidence: 99%

Role of Descending Serotonergic Fibers in the Development of Pathophysiology after Spinal Cord Injury (SCI): Contribution to Chronic Pain, Spasticity, and Autonomic Dysreflexia

Fauss

Hudson

Grau

2022

Biology

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As the nervous system develops, nerve fibers from the brain form descending tracts that regulate the execution of motor behavior within the spinal cord, incoming sensory signals, and capacity to change (plasticity). How these fibers affect function depends upon the transmitter released, the receptor system engaged, and the pattern of neural innervation. The current review focuses upon the neurotransmitter serotonin (5-HT) and its capacity to dampen (inhibit) neural excitation. A brief review of key anatomical details, receptor types, and pharmacology is provided. The paper then considers how damage to descending serotonergic fibers contributes to pathophysiology after spinal cord injury (SCI). The loss of serotonergic fibers removes an inhibitory brake that enables plasticity and neural excitation. In this state, noxious stimulation can induce a form of over-excitation that sensitizes pain (nociceptive) circuits, a modification that can contribute to the development of chronic pain. Over time, the loss of serotonergic fibers allows prolonged motor drive (spasticity) to develop and removes a regulatory brake on autonomic function, which enables bouts of unregulated sympathetic activity (autonomic dysreflexia). Recent research has shown that the loss of descending serotonergic activity is accompanied by a shift in how the neurotransmitter GABA affects neural activity, reducing its inhibitory effect. Treatments that target the loss of inhibition could have therapeutic benefit.

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“…Considerable interest has been devoted to 5-HT 1A , 5-HT 2A , and 5-HT 2C in terms of their anatomical and functional changes, likely due to their direct involvement in regulating motoneuronal excitability and functional recovery after SCI [ 80 , 85 ]. In the chronic phase of SCI, a number of 5-HT receptors are upregulated in the spinal cord.…”

Section: Effect Of Rehabilitation On Spinal Network Below the Injurymentioning

confidence: 99%

Exercise-Induced Plasticity in Signaling Pathways Involved in Motor Recovery after Spinal Cord Injury

Bilchak

Caron

Côté

2021

IJMS

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Spinal cord injury (SCI) leads to numerous chronic and debilitating functional deficits that greatly affect quality of life. While many pharmacological interventions have been explored, the current unsurpassed therapy for most SCI sequalae is exercise. Exercise has an expansive influence on peripheral health and function, and by activating the relevant neural pathways, exercise also ameliorates numerous disorders of the central nervous system (CNS). While the exact mechanisms by which this occurs are still being delineated, major strides have been made in the past decade to understand the molecular underpinnings of this essential treatment. Exercise rapidly and prominently affects dendritic sprouting, synaptic connections, neurotransmitter production and regulation, and ionic homeostasis, with recent literature implicating an exercise-induced increase in neurotrophins as the cornerstone that binds many of these effects together. The field encompasses vast complexity, and as the data accumulate, disentangling these molecular pathways and how they interact will facilitate the optimization of intervention strategies and improve quality of life for individuals affected by SCI. This review describes the known molecular effects of exercise and how they alter the CNS to pacify the injury environment, increase neuronal survival and regeneration, restore normal neural excitability, create new functional circuits, and ultimately improve motor function following SCI.

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Serotonergic influences on locomotor circuits

Cited by 16 publications

References 76 publications

Serotonergic Modulation of Locomotor Activity From Basal Vertebrates to Mammals

Serotonergic Modulation of Locomotor Activity From Basal Vertebrates to Mammals

Role of Descending Serotonergic Fibers in the Development of Pathophysiology after Spinal Cord Injury (SCI): Contribution to Chronic Pain, Spasticity, and Autonomic Dysreflexia

Exercise-Induced Plasticity in Signaling Pathways Involved in Motor Recovery after Spinal Cord Injury

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