Spontaneous Release Regulates Synaptic Scaling in the Embryonic Spinal Network In Vivo
| Autor: | Peter Wenner, Carlos Gonzalez-Islas, Casie Lindsly, Miguel Angel Garcia-Bereguiain |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cyclopropanes Male Movement Glycine Action Potentials Chick Embryo Neurotransmission Biology 03 medical and health sciences 0302 clinical medicine Chlorides Synaptic augmentation Homeostatic plasticity Metaplasticity Animals Homeostasis Anesthetics Local gamma-Aminobutyric Acid Motor Neurons Neurotransmitter Agents Synaptic scaling GABAA receptor General Neuroscience Age Factors Lidocaine Articles Synaptic Potentials Receptors GABA-A 030104 developmental biology Nicotinic agonist Synaptic fatigue Spinal Cord Synapses Anticonvulsants Female Nerve Net Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 36(27) |
| ISSN: | 1529-2401 |
| Popis: | Homeostatic plasticity mechanisms maintain cellular or network spiking activity within a physiologically functional range through compensatory changes in synaptic strength or intrinsic cellular excitability. Synaptic scaling is one form of homeostatic plasticity that is triggered after blockade of spiking or neurotransmission in which the strengths of all synaptic inputs to a cell are multiplicatively scaled upward or downward in a compensatory fashion. We have shown previously that synaptic upscaling could be triggered in chick embryo spinal motoneurons by complete blockade of spiking or GABA A receptor (GABA A R) activation for 2 d in vivo . Here, we alter GABA A R activation in a more physiologically relevant manner by chronically adjusting presynaptic GABA release in vivo using nicotinic modulators or an mGluR2 agonist. Manipulating GABA A R activation in this way triggered scaling in a mechanistically similar manner to scaling induced by complete blockade of GABA A Rs. Remarkably, we find that altering action-potential (AP)-independent spontaneous release was able to fully account for the observed bidirectional scaling, whereas dramatic changes in spiking activity associated with spontaneous network activity had little effect on quantal amplitude. The reliance of scaling on an AP-independent process challenges the plasticity9s relatedness to spiking in the living embryonic spinal network. Our findings have implications for the trigger and function of synaptic scaling and suggest that spontaneous release functions to regulate synaptic strength homeostatically in vivo . SIGNIFICANCE STATEMENT Homeostatic synaptic scaling is thought to prevent inappropriate levels of spiking activity through compensatory adjustments in the strength of synaptic inputs. Therefore, it is thought that perturbations in spike rate trigger scaling. Here, we find that dramatic changes in spiking activity in the embryonic spinal cord have little effect on synaptic scaling; conversely, alterations in GABA A receptor activation due to action-potential-independent GABA vesicle release can trigger scaling. The findings suggest that scaling in the living embryonic spinal cord functions to maintain synaptic strength and challenge the view that scaling acts to regulate spiking activity homeostatically. Finally, the results indicate that fetal exposure to drugs that influence GABA spontaneous release, such as nicotine, could profoundly affect synaptic maturation. |
| Databáze: | OpenAIRE |
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