Chronic intermittent ethanol exposure alters CA1 synaptic transmission in rat hippocampal slices

Nelson, Thomas E.; Ur, C. L.; Gruol, Donna L.

doi:10.1016/s0306-4522(99)00336-x

“…Collectively, the results of these studies support the notion that ethanol inhibits glutamate release from Schaffer collaterals/commissural axons to CA1 pyramidal neurons. However, their findings are inconsistent with those of other studies indicating that ethanol does not affect AMPAR-mediated EPSCs evoked by Schaffer collateral/ commissural pathway stimulation in CA1 pyramidal neurons and interneurons in slices from rats older than P12 (Lovinger et al, 1990;Morrisett et al, 1991;Morrisett and Swartzwelder, 1993;Nelson et al, 1999;Carta et al, 2003). Future work will be required to establish the reasons for the discrepancies between these studies.…”

Section: Ethanol Affects Glutamatergic Synaptic Currents In Neonatal contrasting

confidence: 55%

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

Mameli¹,

Zamudio²,

Carta³

et al. 2005

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Ethanol exposure during fetal development is a leading cause of learning disabilities. Studies suggest that it alters learning and memory by permanently damaging the hippocampus. It is generally assumed that this is mediated, in part, via alterations in glutamatergic transmission. Although NMDA receptors are presumed to be the most sensitive targets of ethanol in immature neurons, this issue has not been explored in the developing hippocampus. We performed whole-cell patch-clamp recordings in hippocampal slices from neonatal rats. Unexpectedly, we found that acute ethanol (10 -50 mM) exposure depresses inward currents elicited by local application of exogenous AMPA, but not NMDA, in CA3 pyramidal neurons. These findings revealed a direct effect of ethanol on postsynaptic AMPA receptors. Ethanol significantly decreased the amplitude of both AMPA and NMDA receptor-mediated EPSCs evoked by electrical stimulation. This effect was associated with an increase in the paired-pulse ratio and a decrease in the frequency of miniature EPSCs driven by depolarization of axonal terminals. These findings demonstrate that ethanol also acts at the presynaptic level. -Conotoxin-GVIA occluded the effect of ethanol on NMDA EPSCs, indicating that ethanol decreases glutamate release via inhibition of N-type voltage-gated Ca 2ϩ channels. In more mature rats, ethanol did not affect the probability of glutamate release or postsynaptic AMPA receptor-mediated currents, but it did inhibit NMDA-mediated currents. We conclude that the mechanism by which ethanol inhibits glutamatergic transmission is age dependent and challenge the view that postsynaptic NMDA receptors are the primary targets of ethanol early in development.

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“…proven invaluable in studies investigating the effects of fetal alcohol exposure (Bellinger et al, 1999) and chronic alcohol exposure and withdrawal on excitatory (Morrisett, 1994;Nelson et al, 1999) and inhibitory (Rogers and Hunter, 1992;Kang et al, 1996) synaptic transmission.…”

Section: Controls > Alcoholicsmentioning

confidence: 99%

“…Control rats are maintained in the same type of chambers but are exposed to air only. This method can produce blood alcohol levels as high as 0.2-0.3 g/dl (Gruol et al, 1998;Nelson et al, 1999), and it has been widely used to study the chronic effects of ethanol exposure on neurotransmitter receptors in developing and adult animals (Gruol et al, 1998; Jarvis and Becker, 1998;Nelson et al, 1999).…”

Section: Long-tirm Exposure To Ethanol Of Cultured Cells and Animalsmentioning

confidence: 99%

“…Control rats are maintained in the same type of chambers but are exposed to air only. This method can produce blood alcohol levels as high as 0.2-0.3 g/dl (Gruol et al, 1998;Nelson et al, 1999), and it has been widely used to study the chronic effects of ethanol exposure on neurotransmitter receptors in developing and adult animals (Gruol et al, 1998; Jarvis and Becker, 1998;Nelson et al, 1999).Ethanol can also be administered to animals by gastric intubation, but it must be kept in mind that blood alcohol levels cannot be sustained throughout the day with this method unless the animals are intubated multiple times (Lieber et al, 1989). Relatively short-term treatments (three daily intubations for 6 d) have been successfully used by Ticku and collaborators to study the effects of long-term ethanol exposure on NMDA receptor subunit expression in the rat brain (for example see Kalluri et al, 1998).…”

mentioning

confidence: 99%

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Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

Valenzuela¹

2004

0

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SUPPLEMENTARY NOTES 12a. DISTRIBUTION /AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited 12b. DISTRIBUTION CODE Abstract (Maximum 200 Words) labstract should contain no proprietary or confidential information)We have been testing the hypothesis that chronic alcohol exposure alters expression and/or function of kainate receptors (KA-Rs) in the hippocampus. KA-Rs control hippocampal excitability and an ethanol-induced upregulation of KA-Rs could contribute to the hyperexcitability associated with alcohol withdrawal. Unexpectedly, Western immunoblotting and immunohistochemical studies have demonstrated that chronic ethanol exposure does not upregulate KA-R subunit expression. However, studies with cultured neurons suggest that alcohol withdrawal itself, but not chronic ethanol exposure, upregulates KA-R function. Therefore, we are now focusing our efforts at testing if this is also true for animals exposed to ethanol. We have switched to a different method of alcohol exposure; we are using the inhalation route, which reproducibly produces high ethanol levels. We are currently processing brain sections from control rats and rats withdrawn from a 14-day inhalational ethanol exposure paradigm. These sections will be immunostained with anti-GluR6/7 antibodies and will be used for radioligand binding experiments. We have also characterized the acute effects of ethanol on the function of interneuronal KA-Rs. Moreover, a preliminary experiment with hippocampal slices from rats withdrawn from a 6-day inhalational exposure paradigm suggests that the function of these receptors is upregulated. During the last year of support, we will concentrate on characterizing the function of KA-Rs in the CA1 and CAS regions in alcohol withdrawn rats. Alcohol-related medical disorders affect many organs and systems of the body, including the central nervous system (CNS). As with other drugs of abuse, long-term alcohol ingestion results in the development of tolerance, addiction, and dependence. Alcohol produces these effects by altering the actions of neurotransmitters and their receptors in the brain. Chronic ethanol exposure has complex and long-lasting effects on the function and/or expression of a myriad of neurotransmitter receptors and their modulators. A group of proteins affected by chronic ethanol exposure are hgand-gated ion channels such as the glutamatergic ionotropic receptors. Glutamate activates three major classes of ionotropic receptors. These three major types of channels are the NMD A, AMPA and kainate receptors (KA-Rs). The purpose of this proposal is to test whether or not chronic ethanol exposure results in alterations in subunit expression and/or function of KA-Rs in the hippocampus. Maladaptive changes in hippocampal KA-R expression could contribute to the pathophysiology of alcohol withdrawal syndrome. The alcohol withdrawal syndrome is associated with neuronal hyperexcitabiUty and seizures. Since kainate receptors are important regulators of excitability in the hippocampus, upregulation o...

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“…Other important advantages of this technique are that it can be carried out for relatively long periods of time and extracellular responses tend to be more stable and less variable than those recorded from individual cells, as they represent the summed activity of large populations of neurons. The stabiUty and relatively low variabiUty of these recordings makes them particularly well suited for studies that require long-term monitoring of a synaptic responses, such as during alcohol withdrawal (Thomas et al, 1998B) or when carrying out inter-subject comparisons (Nelson et al, 1999). Finally, some extracellular recording methods have been adapted to record extracellular activity in vivo in anesthetized and awake, freely moving animals (see Chapters 9 and 10).…”

Section: Extracellular Recordingmentioning

confidence: 99%

Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

Valenzuela¹,

Savage²,

Weiner³

2002

0

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SUPPLEMENTARY NOTES 12a. DISTRIBUTION /AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited 12b. DISTRIBUTION CODE Abstract (Maximum 200 Words) labstract should contain no proprietary or confidential information)We have been testing the hypothesis that chronic alcohol exposure alters expression and/or function of kainate receptors (KA-Rs) in the hippocampus. KA-Rs control hippocampal excitability and an ethanol-induced upregulation of KA-Rs could contribute to the hyperexcitability associated with alcohol withdrawal. Unexpectedly, Western immunoblotting and immunohistochemical studies have demonstrated that chronic ethanol exposure does not upregulate KA-R subunit expression. However, studies with cultured neurons suggest that alcohol withdrawal itself, but not chronic ethanol exposure, upregulates KA-R function. Therefore, we are now focusing our efforts at testing if this is also true for animals exposed to ethanol. We have switched to a different method of alcohol exposure; we are using the inhalation route, which reproducibly produces high ethanol levels. We are currently processing brain sections from control rats and rats withdrawn from a 14-day inhalational ethanol exposure paradigm. These sections will be immunostained with anti-GluR6/7 antibodies and will be used for radioligand binding experiments. We have also characterized the acute effects of ethanol on the function of interneuronal KA-Rs. Moreover, a preliminary experiment with hippocampal slices from rats withdrawn from a 6-day inhalational exposure paradigm suggests that the function of these receptors is upregulated. During the last year of support, we will concentrate on characterizing the function of KA-Rs in the CA1 and CAS regions in alcohol withdrawn rats. Alcohol-related medical disorders affect many organs and systems of the body, including the central nervous system (CNS). As with other drugs of abuse, long-term alcohol ingestion results in the development of tolerance, addiction, and dependence. Alcohol produces these effects by altering the actions of neurotransmitters and their receptors in the brain. Chronic ethanol exposure has complex and long-lasting effects on the function and/or expression of a myriad of neurotransmitter receptors and their modulators. A group of proteins affected by chronic ethanol exposure are hgand-gated ion channels such as the glutamatergic ionotropic receptors. Glutamate activates three major classes of ionotropic receptors. These three major types of channels are the NMD A, AMPA and kainate receptors (KA-Rs). The purpose of this proposal is to test whether or not chronic ethanol exposure results in alterations in subunit expression and/or function of KA-Rs in the hippocampus. Maladaptive changes in hippocampal KA-R expression could contribute to the pathophysiology of alcohol withdrawal syndrome. The alcohol withdrawal syndrome is associated with neuronal hyperexcitabiUty and seizures. Since kainate receptors are important regulators of excitability in the hippocampus, upregulation o...

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Chronic intermittent ethanol exposure alters CA1 synaptic transmission in rat hippocampal slices

Cited by 30 publications

References 41 publications

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

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