Activity-dependent modulation of GABAergic synapses in developing rat spinal networks in vitro.
The role of activity-dependent plasticity in modulating inhibitory synapses was investigated in embryonic rat spinal cord slice cultures, by chronic exposure to non-NMDA receptor blockers. GABAergic synaptic efficacy in control and chronic-treated cultures was investigated by patch-recordings from visually identified spinal interneurons. In both culture groups proximal stimulation induced the appearance of postsynaptic currents (PSCs), which were fully antagonized by 20 microM bicuculline application and reverse polarity at potential values close to those reported for spontaneous GABAergic PSCs. In chronically treated cells GABAergic evoked PSCs displayed a larger failure rate and a smaller coefficient of variation of mean PSC amplitude, when compared to controls. As opposed to controls, chronic GABAergic evoked PSCs did not facilitate upon paired-pulse stimulation. Facilitation at chronic synapses was observed when extracellular calcium levels were decreased below physiological values (< 2 mM). Kainate was used to disclose any functional differences between control and treated slices. In accordance with the presynaptic action of kainate, the application of this drug along with GYKI, an AMPA receptor selective antagonist, changed, with analogous potency, short-term plasticity of GABAergic synapses from control and treated cultures. Nevertheless, in chronic cultures, the downstream effects of such activation unmasked short-term depression. Ultrastructural analysis of synapses in chronically treated cultures showed a reduction both in symmetric synapses and in the number of vesicles at symmetric terminals. Thus, based on electrophysiological and ultrastructural data, it could be suggested that during the development of spinal circuits, GABAergic synapses are modulated by glutamatergic transmission, and thus implying that excitatory transmission regulates the strength of GABAergic synapses.
Rosato-Siri
Marcelo
M
Biophysics Sector and Istituto Nazionale di Fisica della Materia Unit, International School for Advanced Studies (SISSA), via Beirut 2-4, 34014 Trieste, Italy.
Grandolfo
Micaela
M
Ballerini
Laura
L
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005333:Fetus; D018698:Glutamic Acid / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008854:Microscopy, Electron; D009415:Nerve Net / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D005680:gamma-Aminobutyric Acid