Abstract
Physical exercise stimulates adult neurogenesis, yet the underlying mechanisms remain poorly understood. A fundamental component of the innate neuroregenerative capacity of zebrafish is the proliferative and neurogenic ability of the neural stem/progenitor cells. Here, we show that in the intact spinal cord, this plasticity response can be activated by physical exercise by demonstrating that the cholinergic neurotransmission from spinal locomotor neurons activates spinal neural stem/progenitor cells, leading to neurogenesis in the adult zebrafish. We also show that GABA acts in a non-synaptic fashion to maintain neural stem/progenitor cell quiescence in the spinal cord and that training-induced activation of neurogenesis requires a reduction of GABAA receptors. Furthermore, both pharmacological stimulation of cholinergic receptors, as well as interference with GABAergic signaling, promote functional recovery after spinal cord injury. Our findings provide a model for locomotor networks’ activity-dependent neurogenesis during homeostasis and regeneration in the adult zebrafish spinal cord.
Highlights
Physical exercise stimulates adult neurogenesis, yet the underlying mechanisms remain poorly understood
Here we revealed an adaptive mechanism by which physical activity dynamically modulates adult neurogenesis mediated by ACh and GABA neurotransmitters
While activation of neural stem/progenitor cells (NSPCs) relies on an increased synaptic cholinergic input and is independent of the number of cholinergic receptors, insensitivity to non-synaptic GABAergic signaling[3,8] is achieved by reducing the abundance of GABAA receptors (Fig. 7)
Summary
Physical exercise stimulates adult neurogenesis, yet the underlying mechanisms remain poorly understood. We show that GABA acts in a non-synaptic fashion to maintain neural stem/ progenitor cell quiescence in the spinal cord and that training-induced activation of neurogenesis requires a reduction of GABAA receptors. Both pharmacological stimulation of cholinergic receptors, as well as interference with GABAergic signaling, promote functional recovery after spinal cord injury. At the level of spinal locomotor circuits, several classes of premotor interneurons use specific neurotransmitters, including glutamate, γ-aminobutyric acid (GABA), glycine, and acetylcholine (ACh), to mediate their functions[22] It is unknown whether these neurotransmitters released during locomotion can directly affect the neural stem/progenitor cells (NSPCs) within the spinal cord. The results demonstrate that spinal network activity plays a crucial role in modulating non-motor and non-neuronal functions in the nervous system besides generating motor behaviors
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