Anti-homeostatic synaptic plasticity of glycine receptor function after chronic strychnine in developing cultured mouse spinal neurons

Carrasco MA; Castro PA; Sepulveda, FJ; Cuevas, M.; Tapia, JC; Izaurieta, P; van Zundert, B; Aguayo, LG

Abstract

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 γ-aminobutyric acid (GABAA) 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. © 2007 The Authors.

Más información

Título según WOS: Anti-homeostatic synaptic plasticity of glycine receptor function after chronic strychnine in developing cultured mouse spinal neurons
Título según SCOPUS: Anti-homeostatic synaptic plasticity of glycine receptor function after chronic strychnine in developing cultured mouse spinal neurons
Título de la Revista: JOURNAL OF NEUROCHEMISTRY
Volumen: 100
Número: 5
Editorial: WILEY-BLACKWELL
Fecha de publicación: 2007
Página de inicio: 1143
Página final: 1154
Idioma: English
URL: http://doi.wiley.com/10.1111/j.1471-4159.2006.04306.x
DOI:

10.1111/j.1471-4159.2006.04306.x

Notas: ISI, SCOPUS