Anti-homeostatic synaptic plasticity of glycine receptor function after chronic strychnine in developing cultured mouse spinal neurons.
In this study, we describe a novel form of anti-homeostatic plasticity produced after culturing spinal neurons with strychnine, but not bicuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Strychnine caused a large increase in network excitability, detected as spontaneous synaptic currents and calcium transients. The calcium transients were associated with action potential firing and activation of gamma-aminobutyric acid (GABA(A)) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors as they were blocked by tetrodotoxin (TTX), bicuculline, and CNQX. After chronic blockade of glycine receptors (GlyRs), the frequency of synaptic transmission showed a significant enhancement demonstrating the phenomenon of anti-homeostatic plasticity. Spontaneous inhibitory glycinergic currents in treated cells showed a fourfold increase in frequency (from 0.55 to 2.4 Hz) and a 184% increase in average peak amplitude compared with control. Furthermore, the augmentation in excitability accelerated the decay time constant of miniature inhibitory post-synaptic currents. Strychnine caused an increase in GlyR current density, without changes in the apparent affinity. These findings support the idea of a post-synaptic action that partly explains the increase in synaptic transmission. This phenomenon of synaptic plasticity was blocked by TTX, an antibody against brain-derived neurotrophic factor (BDNF) and K252a suggesting the involvement of the neuronal activity-dependent BDNF-TrkB signaling pathway. These results show that the properties of GlyRs are regulated by the degree of neuronal activity in the developing network.
Carrasco
M A
MA
Laboratory of Neurophysiology, Department of Physiology, University of Concepción, Concepción, Chile.
Castro
P A
PA
Sepulveda
F J
FJ
Cuevas
M
M
Tapia
J C
JC
Izaurieta
P
P
van Zundert
B
B
Aguayo
L G
LG
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D020813:Receptor, trkB / Q000502:physiology; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013331:Strychnine / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission
D019208:Brain-Derived Neurotrophic Factor; D018009:Receptors, Glycine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D020813:Receptor, trkB; D013331:Strychnine; D002118:Calcium; D001640:Bicuculline