Binge ethanol exposure delays development of GABAergic miniature postsynaptic currents in septal neurons

详细信息    查看全文

• 作者：DuBois ; Dustin W. ; Parrish ; Alan R. ; Trzeciakowski ; Jerome P. ; Frye ; Gerald D.
• 关键词：GABA_A receptor ; GABA_B receptor ; Fetal alcohol syndrome ; Miniature inhibitory postsynaptic current ; Development ; Picrotoxin
• 刊名：Developmental Brain Research
• 出版年：2004
• 出版时间：September 17, 2004
• 年：2004
• 卷：152
• 期：2
• 页码：199-212
• 全文大小：899 K

文摘

Whole cell GABA_AR currents of septal neurons isolated from rat pups increase rapidly during the first weeks of life when inhibitory synapses are forming. Early postnatal binge ethanol intubation on days 4aaa9 delays this maturational up-regulation in septal neurons isolated several days later suggesting inhibitory synapse formation could be disrupted [S.aaaH. Hsiao, J.L. Acevedo, D.W. DuBois, K.R. Smith, J.R. West, G.D. Frye, Early postnatal ethanol intubation blunts GABA_A receptor upregulation and modifies 3aa-hydroxy-5aa-pregnan-20-one sensitivity in rat MS/DB neurons, Brain Res. Dev. Brain Res. 130 (2001) 25aaa40]. Surprisingly, whole cell GABA_AR function does not increase rapidly when septal neurons are grown for the same period in vitro and is not blunted by comparable ethanol exposure of the cultures [S.aaaH. Hsiao, D.W. DuBois, R.C. Miranda, G.D. Frye, Critically timed ethanol exposure reduces GABA_AR function on septal neurons developing in vivo but not in vitro, Brain Res Dev. Brain Res. 1008 (2004) 69aaa80]. Because GABAergic miniature postsynaptic currents (mPSCs) show parallel patterns of maturation whether cortical neurons are growing in vivo or in vitro [D.D. Dunning, C.L. Hoover, I. Soltesz, M.A. Smith, D.K. ODowd, GABA_A receptor-mediated miniature postsynaptic currents and aaaaasubunit expression in developing cortical neurons, J. Neurophysiol. 82 (1999) 3286aaa3297], we examined the impact of binge ethanol exposure on synaptic receptors activated by these currents in septal cultures. Binge ethanol treatment of embryonic septal neurons over 6aaa11 days in vitro (DIV) slightly reduced GABA_AR-mediated mPSC amplitude and frequency, but also substantially slowed decay kinetics when mPSCs were recorded later on DIV 13aaa18. Decreased frequency and slowed mPSC decay kinetics after ethanol were consistent with parameters measured in immature neurons. Untreated septal neurons exhibited decreased mPSC amplitude and frequency with acute 30aaa100 mM ethanol, without changing decay kinetics suggesting a direct inhibition of postsynaptic receptors. Sustained inhibition of GABA_ARs with 100 aaM picrotoxin on DIV 6aaa11 decreased mPSC amplitude and frequency and slowed decay kinetics similar to binge ethanol exposure. These results suggest that binge ethanol exposure delays mPSC maturation by interfering with trophic postsynaptic GABA_AR signaling during the early development of septal neurons.