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.

Drunken Membranes: Short-Chain Alcohols Alter Fusion of Liposomes to Planar Lipid Bilayers

“…Elucidating the molecular targets of alcohol's action in brain and linking these sites to specific behavioral actions of ethanol is critical for understanding alcohol use, abuse, and dependence. The exact pathways whereby ethanol exerts its effect on the brain are controversial, but likely involve a constellation of effects on membrane proteins (3)(4)(5), electrical and chemical synaptic transmission, and fluidizing of the lipid membrane. Being a simple molecule (C 2 H 6 O) it would be expected that ethanol acts through a general mechanism rather than specific interactions such as antigen-antibody binding.…”

“…But despite decades of investigation, the evidence is inconclusive for any specific molecular target for ethanol on any protein (for reviews see (6,7)). Many potential protein targets have been identified (4,8) including voltage-gated Na þ channels (9), adenylyl cyclase (10,11), guanine nucleotide binding protein G s (12), the GLT1 glutamate transporter (13), gap junctions (14), g-aminobutyric acid (GABA) A receptors (6), n-methyl-daspartate (NMDA) receptors (15), nicotinic acetylcholine receptor (nAChR) channels (16,17), and the cannabinoid receptor 1 (18). One system within the brain that appears to be sensitive to alcohol dependence is the endocannabinoid system (for review see (19)).…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…Repetitive patterned activation of afferent inputs to postsynaptic neurons induces longlasting changes in the efficacy of synaptic transmission. The most common forms of these changes, LTP and LTD, have also been examined after acute ethanol (McCool, 2011). Consistent with the inhibition of NMDARs at relevant ethanol concentrations, acute ethanol inhibits induction of LTP at various synapses and experimental preparations, such as Schaffer collateral inputs to the CA1 pyramidal neurons in the HC .…”

From Signaling Pathways to Behavior

“…Drug and alcohol addiction is a pathological form of learning and memory (Kauer & Malenka, 2007;Luscher & Malenka, 2011;McCool, 2011); therefore, it is highly likely that the mTORC1 signaling pathway as well as other signaling pathways that control synaptic plasticity and learning and memory events are activated in response to alcohol.…”