title: Blockade and recovery of spontaneous rhythmic activity after application of neurotransmitter antagonists to spinal networks of the chick embryo.
abstract: We studied the regulation of spontaneous activity in the embryonic (day 10-11) chick spinal cord. After bath application of either an excitatory amino acid (AP-5 or CNQX) and a nicotinic cholinergic (DHbetaE or mecamylamine) antagonist, or glycine and GABA receptor (bicuculline, 2-hydroxysaclofen, and strychnine) antagonists, spontaneous activity was blocked for a period (30-90 min) but then reappeared in the presence of the drugs. The efficacy of the antagonists was assessed by their continued ability to block spinal reflex pathways during the reappearance of spontaneous activity. Spontaneous activity ceased over the 4-5 hour monitoring period when both sets of antagonists were applied together. After application of glycine and GABA receptor antagonists, the frequency of occurrence of spontaneous episodes slowed and became highly variable. By contrast, during glutamatergic and nicotinic cholinergic blockade, the frequency of occurrence of spontaneous episodes initially slowed and then recovered to stabilize near the predrug level of activity. Whole-cell recordings made from ventral spinal neurons revealed that this recovery was accompanied by an increase in the amplitude of spontaneously occurring synaptic events. We also measured changes in the apparent equilibrium potential of the rhythmic, synaptic drive of ventral spinal neurons using voltage or discontinuous current clamp. After excitatory blockade, the apparent equilibrium potential of the rhythmic synaptic drive shifted approximately 10 mV more negative to approximately -30 mV. In the presence of bicuculline, the apparent equilibrium potential of the synaptic drive shifted toward the glutamate equilibrium potential. Considered with other evidence, these findings suggest that spontaneous rhythmic output is a general property of developing spinal networks, and that GABA and glycinergic networks alter their function to compensate for the blockade of excitatory transmission.
authors.affiliation: Section on Developmental Neurobiology, Laboratory of Neural Control, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: N
authors.initials: N
authors.lastname: Chub
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Donovan
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002642:Chick Embryo; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D005071:Evoked Potentials / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors* / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010507:Periodicity; D013116:Spinal Cord / Q000166:cytology*; D013331:Strychnine / Q000494:pharmacology
chemical_list: D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents; D018377:Neurotransmitter Agents; D018733:Nicotinic Antagonists; C052329:phaclofen; D004079:Dihydro-beta-Erythroidine; D008464:Mecamylamine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001418:Baclofen; D013331:Strychnine; D005998:Glycine; C057491:2-hydroxysaclofen; D001640:Bicuculline