Ethanol modulation of synaptic plasticity

Abstract

Synaptic plasticity in the most general terms represents the flexibility of neurotransmission in response to neuronal activity. Synaptic plasticity is essential both for the moment-by-moment modulation of neural activity in response to dynamic environmental cues and for long-term learning and memory formation. These temporal characteristics are served by an array of pre- and post-synaptic mechanisms that are frequently modulated by ethanol exposure. This modulation likely makes significant contributions to both alcohol abuse and dependence. In this review, I discuss the modulation of both short-term and long-term synaptic plasticity in the context of specific ethanol-sensitive cellular substrates. A general discussion of the available preclinical, animal-model based neurophysiology literature provides a comparison between results from in vitro and in vivo studies. Finally, in the context of alcohol abuse and dependence, the review proposes potential behavioral contributions by ethanol modulation of plasticity.

Figure 1. Chronic ethanol exposure occludes distinct forms of long-term synaptic plasticity in the lateral/basolateral amygdala

(A) The panels are reprinted from Biological Psychiatry (58), Stephens et al., “Repeated ethanol exposure and withdrawal impairs human fear conditioning and depresses long-term potentiation in rat amygdala and hippocampus”, 392–400, Copyright (2005), with permission from Elsevier. (Left) Representation of the horizontal slice preparation used in this study illustrates the relationships between the recording electrode (R), the stimulator (S), the lateral amygdala (LA), and anatomical boundaries like the external capsule. (Right) Theta burst stimulation (TBS) of the external capsule caused robust long-term potentiation of synaptic responses in slices prepared from control animals (M) while repeated withdrawal from a chronic exposure to an ethanol-containing liquid diet (F) reduced the magnitude of this form of plasticity. (B) Panels reprinted from Alcohol (43), Läck et al., “Chronic ethanol and withdrawal effects on kainate receptor-mediated excitatory neurotransmission in the rat basolateral amygdala”, 25–33, Copyright (2009), with permission from Elsevier. (Left) Sample fEPSP responses recorded in basolateral amygdala in control brain slices (CON) or 24hr after a chronic intermittent exposure to ethanol vapor (24WD). Kainate receptor-dependent long-term synaptic potentiation was initiated by a 15min exposure to the agonist ATPA ((RS)-2-Amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid; 5 μM). (Right) The magnitude of ATPA-induced LTP was significantly depressed by chronic ethanol exposure (not shown) and withdrawal.

Figure 2. Chronic intermittent ethanol exposure and withdrawal upregulate the synaptic function of AMPA-type glutamate receptors in the lateral/basolateral amygdala

The figure is republished with permission of the American Physiological Society from “Chronic ethanol and withdrawal differentially modulate pre- and postsynaptic function at glutamatergic synapses in rat basolateral amygdala”, Läck et al., Journal of Neurophysiology 98(6), 3185–96, 2007; permission conveyed through Copyright Clearance Center, Inc. (A) Exemplar traces of spontaneous glutamatergic synaptic activity recorded from lateral/basolateral amygdala (BLA) principal neurons using whole-cell patch-clamp electrophysiology. In the presence of the voltage-gated sodium channel blocker tetrodotoxin, the resulting miniature EPSCs (mEPSCs) are smaller in amplitude and occur less frequently. (B) Exemplar mEPSCs recorded from control (CON) BLA slices, immediately following a chronic intermittent ethanol exposure (CIE), or 24hr after withdrawal from CIE (WD). (C) Summary of mEPSC amplitude data from the three treatment groups. mEPSC amplitude was significantly greater in WD neurons compared to both CON and CIE. (D) The charge carried by mEPSCs was not significantly different between the treatment groups, largely due to an increase in the decay rate of individual mEPSCs recorded from WD BLA neurons (not shown). (E&F) The interval between mEPSCs was significantly shorter in recordings from WD BLA neurons compared to the other treatment groups.