title: The spinal GABAergic system is a strong modulator of burst frequency in the lamprey locomotor network.
abstract: The spinal network coordinating locomotion is comprised of a core of glutamate and glycine interneurons. This network is modulated by several transmitter systems including spinal GABA interneurons. The purpose of this study is to explore the contribution of GABAergic neurons to the regulation of locomotor burst frequency in the lamprey model. Using gabazine, a competitive GABAA antagonist more specific than bicuculline, the goal was to provide a detailed analysis of the influence of an endogenous activation of GABAA receptors on fictive locomotion, as well as their possible interaction with GABAB and involvement of GABAC receptors. During N-methyl-D-aspartate (NMDA)-induced fictive locomotion (ventral root recordings in the isolated spinal cord), gabazine (0.1-100 microM) significantly increased the burst rate up to twofold, without changes in regularity or "burst quality." Gabazine had a proportionately greater effect at higher initial burst rates. Picrotoxin (1-7.5 microM), a less selective GABAA antagonist, also produced a pronounced increase in frequency, but at higher concentrations, the rhythm deteriorated, likely due to the unspecific effects on glycine receptors. The selective GABAB antagonist CGP55845 also increased the frequency, and this effect was markedly enhanced when combined with the GABAA antagonist gabazine. The GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA) had no effect on locomotor bursting. Thus the spinal GABA system does play a prominent role in burst frequency regulation in that it reduces the burst frequency by < or =50%, presumably due to presynaptic and soma-dendritic effects documented previously. It is not required for burst generation, but acts as a powerful modulator.
authors.affiliation: Nobel Inst. for Neurophysiology, Dept. of Neuroscience, Karolinska Institutet, SE 17177 Stockholm, Sweden.
authors.forename: David E
authors.initials: DE
authors.lastname: Schmitt
authors.forename: Russell H
authors.initials: RH
authors.lastname: Hill
authors.forename: Sten
authors.initials: S
authors.lastname: Grillner
mesh_terms: D000465:Algorithms; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D007798:Lampreys / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D010721:Phosphinic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D018118:Chloride Channels; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D010852:Picrotoxin; D024681:Potassium Channels, Calcium-Activated; D011412:Propanolamines; D011724:Pyridazines; D011725:Pyridines; D018079:Receptors, GABA; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; C087200:GABA-C receptor; C085075:CGP 55845A; C049853:gabazine