Immature hippocampal neuronal networks do not develop tolerance to the excitatory actions of ethanol

Abstract

EtOH (ethanol) damages the hippocampus, a brain region that is involved in learning and memory processes. The mechanisms responsible for this effect of EtOH are not fully understood. We recently demonstrated that acute EtOH exposure potently stimulates oscillatory activity driven by the excitatory actions of GABA in the CA3 region of the neonatal rat hippocampus. This activity can be recorded during the growth spurt period as giant depolarizing potentials (GDPs). Here, we characterized the effects of prolonged EtOH exposure on GDPs. In the first study, we prepared hippocampal coronal slices from neonatal rats and exposed these to control artificial cerebrospinal fluid (ACSF) or ACSF plus 50 mM EtOH for 3-4 hr. We then performed whole-cell patch-clamp electrophysiological recordings from CA3 pyramidal neurons, which revealed that tolerance to the GDP stimulating effects of EtOH did not occur after continuous exposure. In the second study, we exposed neonatal rats to air or air plus 1.9 g/dL EtOH in vapor chambers for 4 hours/day for 1 or 3 days (neonatal peak blood EtOH concentration = 40-45 mM). We then performed slice electrophysiological studies 24 hours after the end of EtOH exposure and found that there was no statistically significant difference in the acute effect of 50 mM EtOH on GDP frequency in samples from neonates exposed to air or air plus EtOH. These findings indicate that EtOH persistently stimulates network-driven oscillatory activity in the developing hippocampus. We propose that the lack of adaptive response to continuous EtOH exposure could make immature neuronal networks particularly vulnerable to the actions of this agent. Keywords chronic; GABA; excitatory; depolarizing; network; fetal Numerous animal and human studies have demonstrated that EtOH (ethanol) exposure damages the developing hippocampus, leading to deficits in learning and memory (Berman & Hannigan, 2000;Bonthius et al., 2001a;Bonthius et al., 2001b;Mattson et al., 2001;Hamilton et al., 2003). These deficits are a consequence of structural and functional hippocampal abnormalities that persist into adulthood (Sutherland et al., 1997;Krahl et al., 1999;Berman & Hannigan, 2000;Richardson et al., 2002;Savage et al., 2002). Multiple candidate mechanisms could be responsible for these effects of EtOH, including alterations in cellular energetics, gene expression, cell-cell interactions, cell signaling pathways and synaptic Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Goodlett et al., 2005). However, the precise contribution of these mechanisms to EtOH-induced hippocampal damage has ...

Acute oligodendrocyte loss with persistent white matter injury in a third trimester equivalent mouse model of fetal alcohol spectrum disorder

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AMPAR-mediated synaptic transmission in the CA1 hippocampal region of neonatal rats: unexpected resistance to repeated ethanol exposure

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“…Timed-pregnant Sprague-Dawley rats were obtained from Harlan (Indianapolis, IN). Neonatal rat pups and dams were exposed to ethanol vapor as previously described (Galindo and Valenzuela, 2006). Starting on P2, animals were transported to a room housing the ethanol vapor chamber apparatus and weighed prior to exposure.…”

Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis

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