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The Journal of Neuroscience, June 23, 2004, 24(25):5741-5747; doi:10.1523/JNEUROSCI.1181-04.2004

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Behavioral/Systems/Cognitive
High-Frequency Stimulation Induces Ethanol-Sensitive Long-Term Potentiation at Glutamatergic Synapses in the Dorsolateral Bed Nucleus of the Stria Terminalis

Carl Weitlauf,^1,3 Regula E. Egli,² Brad A. Grueter,² and Danny G. Winder^1,2,3,4

¹Neuroscience Graduate Program, ²Department of Molecular Physiology and Biophysics, ³Center for Molecular Neuroscience, and ⁴J. F. Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615

Anatomical and functional data support a critical role for the bed nucleus of the stria terminalis (BNST) in the interaction between stress and alcohol/substance abuse. We report here that neurons of the dorsal anterolateral BNST respond to glutamatergic synaptic input in a synchronized way, such that an interpretable extracellular synaptic field potential can be readily measured. High-frequency stimulation of these glutamatergic inputs evoked NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). We found that an early portion of this LTP is reduced by acute exposure to ethanol in a GABA_A receptor-dependent manner. This effect of ethanol is accompanied by a significant and reversible dose-dependent attenuation of isolated NMDAR signaling and is mimicked by incomplete NMDAR blockade.

Key words: alcohol; alcoholism; synaptic plasticity; stress; anxiety; addiction

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Received Jan 16, 2004; revised May 13, 2004; accepted May 16, 2004.

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