title: Intrinsic activity and positive feedback in motor circuits in organotypic spinal cord slice cultures.
abstract: In co-cultures of embryonic rat spinal cord slices and skeletal muscle, spinal motoneurons innervate muscle fibres and drive muscle contractions. However, multi-electrode array (MEA) recordings show that muscle contractions often appear in the absence of population activity in the spinal cord networks. Such uncorrelated muscle activity persists when the population bursts in the neuronal networks are prevented by un-coupling the network with the glutamatergic antagonists CNQX and D-APV. By contrast, the uncorrelated muscle activity is fully suppressed by the muscular nicotinic antagonist D-tubocurarine. Together, these findings confirm the previous finding that motoneurons drive muscle fibres in this preparation and suggest that they are intrinsically spiking in the absence of synaptic input. Intracellular recordings from spinal neurons support this suggestion. Analysing the correlated muscle activity, we found that in 15% of the population bursts, muscle activity appears at the beginning or before neuronal activity, suggesting that in these cases motoneurons initiate the population activity. Both the total number of population bursts and the percentage of such bursts that are initiated by muscle activity are reduced by a block of nicotinic receptors. Uncorrelated muscle and neuronal activity is reduced by the gap junction blocker carbenoxolone, suggesting that electrical coupling is involved in the generation of this activity. Together, these findings suggest that intrinsic firing of motoneurons may contribute to the activation of population bursts through cholinergic positive feedback loops in cultured spinal networks.
authors.affiliation: Department of Physiology, University of Bern, CH-3012 Bern, Switzerland. magloire@pyl.unibe.ch
authors.forename: Vincent
authors.initials: V
authors.lastname: Magloire
authors.forename: Jürg
authors.initials: J
authors.lastname: Streit
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 / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018920:Coculture Techniques / Q000379:methods; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D006538:Heptanoic Acids / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000502:physiology; D009415:Nerve Net / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology*; D018709:Statistics, Nonparametric; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: C501946:2,2,6,6-tetramethylpiperidin-4-yl heptanoate; D018691:Excitatory Amino Acid Antagonists; D006538:Heptanoic Acids; D018727:Muscarinic Antagonists; D016900:Neurofilament Proteins; D018733:Nicotinic Antagonists; D010880:Piperidines; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001285:Atropine; D002795:Choline O-Acetyltransferase; D002229:Carbenoxolone; D014403:Tubocurarine