Glial-toxin-mediated disruption of spinal cord locomotor network function and its modulation by 5-HT.
While it is established that glial cells actively influence neuronal and synaptic properties, the functional effects of glial-neuronal interactions are still not well understood. To address the role of glia at the network level we have examined the effects of the specific gliotoxin L-aminoadipic acid on the locomotor network output and cellular and synaptic properties in the lamprey spinal cord. The gliotoxic effect of aminoadipic acid was associated with a specific depolarization of glial cells. Aminoadipic acid depolarized the membrane potential of spinal cord neurons, suggesting a functional link between glia and neurons. The depolarization was significantly reduced by glutamate receptor antagonists in adults, but by gap junction blockers in larvae, suggesting a developmental difference in glial-neuronal interactions. Aminoadipic acid also reduced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs), an effect that was not associated with changes in the presynaptic release probability or postsynaptic response to glutamate. These cellular and synaptic effects of aminoadipic acid were associated with disruption of the locomotor network output. This could not be accounted for by changes in glutamate uptake or potassium buffering by glia, suggesting a direct role for glia in the network. Interestingly, we found that the aminoadipic acid-evoked disruption of network activity and reduction of monosynaptic EPSP amplitudes did not occur in the presence of the endogenous spinal modulator 5-HT. These results thus provide evidence for an active functional role for glial cells in spinal cord locomotor networks, and suggest a potential glial modulatory effect of 5-HT.
Baudoux
S
S
Department of Zoology and Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
Parker
D
D
D015074:2-Aminoadipic Acid / Q000633:toxicity*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007798:Lampreys; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D009457:Neuroglia; D012701:Serotonin / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D015074:2-Aminoadipic Acid; D012701:Serotonin; D013779:Tetrodotoxin; D016202:N-Methylaspartate