Long‐term subregion‐specific encoding of enhanced ethanol intake by <scp>D1DR</scp> medium spiny neurons of the nucleus accumbens

Renteria, Rafael; Buske, Tavanna R.; Morrisett, Richard A.

doi:10.1111/adb.12526

Cited by 25 publications

(54 citation statements)

References 48 publications

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“…Specifically, we show that chronic alcohol intake as well as passive alcohol exposure produce an increase in the rectification index of the AMPAR-mediated outward currents in NAc shell MSNs. These findings are in line with recent studies suggesting that contingent and non-contingent alcohol administration increase the rectification index in NAc MSNs (Beckley et al, 2016; Renteria et al, 2017). Importantly, our data suggest that Prosapip1 controls this synaptic modifi-cation.…”

Section: Discussionsupporting

confidence: 93%

Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward

Laguesse

Morisot

Shin

et al. 2017

Neuron

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SUMMARY The mammalian target of rapamycin complex 1 (mTORC1), a transducer of local dendritic translation, participates in learning and memory processes as well as in mechanisms underlying alcohol-drinking behaviors. Using an unbiased RNA-seq approach, we identified Prosapip1 as a novel downstream target of mTORC1 whose translation and consequent synaptic protein expression are increased in the nucleus accumbens (NAc) of mice excessively consuming alcohol. We demonstrate that alcohol-dependent increases in Prosapip1 levels promote the formation of actin filaments, leading to changes in dendritic spine morphology of NAc medium spiny neurons (MSNs). We further demonstrate that Prosapip1 is required for alcohol-dependent synaptic localization of GluA2 lacking AMPA receptors in NAc shell MSNs. Finally, we present data implicating Prosapip1 in mechanisms underlying alcohol self-administration and reward. Together, these data suggest that Prosapip1 in the NAc is a molecular transducer of structural and synaptic alterations that drive and/or maintain excessive alcohol use.

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Section: Discussionsupporting

confidence: 93%

Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward

Laguesse

Morisot

Shin

et al. 2017

Neuron

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“…BECs were maintained by adjusting the flow rate and the loading dose of ethanol and pyrazole. Additional details regarding BEC analysis can be found in Renteria et al, 2018. After the conclusion of each four-day bout of CIE or air exposure, animals were returned to their home cages for 72 hours of withdrawal.…”

Section: Two Bottle Choice and Air/ethanol Vapor Exposurementioning

confidence: 99%

“…Twenty-four hours after CIE vapor exposure, a plasticity induction protocol that normally produces NMDAR-dependent LTD of AMPAR-mediated excitatory postsynaptic currents (EPSCs) in D1-MSNs had no effect on AMPAR-EPSCs, when tested in mice of a Swiss Webster background strain (Jeanes et al, 2014). By contrast, when tested at the same time point post-CIE vapor, the same induction protocol produced long-term potentiation (LTP) of AMPAR-EPSCs in D1-MSNs from mice of a C57BL/6J background strain (Renteria et al, 2018). Differences in the effect of ethanol exposure on plasticity was likely due to C57BL/6J mice, but not Swiss Webster, readily consuming ethanol (Belknap et al, 1993).…”

Section: Introductionmentioning

confidence: 98%

“…Chronic exposure to drugs of abuse and alcohol induces several forms of plasticity within the nucleus accumbens (NAc) (Lüscher and Malenka, 2011;McCool, 2011). For example, several groups have shown that chronic exposure to psychostimulants, heroin, or alcohol alters the expression of NMDA receptor (NMDAR)-dependent long-term depression (LTD) in the NAc (Thomas et al, 2001;Martin et al, 2006;Mao et al, 2009;Kasanetz et al, 2010;Shen and Kalivas, 2012;Abrahao et al, 2013;Jeanes et al, 2014;Spiga et al, 2014;Renteria et al, 2017Renteria et al, , 2018. Alterations in accumbal synaptic plasticity likely play a critical role in the formation of dependence on various drugs of abuse including alcohol.…”

Section: Introductionmentioning

confidence: 99%

“…To investigate this, Renteria et al (2018) measured LTD in the NAc of C57BL/6J mice that exhibited escalated drinking following CIE exposure. The disruption in the nucleus accumbens shell (shNAc) D1-MSN plasticity persisted for up to two weeks and returned to air control levels three weeks after the last ethanol drinking session, mirroring the time course of escalated drinking observed following CIE exposure (Becker and Lopez, 2004;Renteria et al, 2018). The loss of LTD was also accompanied by an increase in the rectification index of AMPAR-mediated currents in D1-MSNs of the shNAc, 24 h after the last drinking session.…”

Section: Introductionmentioning

confidence: 99%

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Ethanol Experience Enhances Glutamatergic Ventral Hippocampal Inputs to D1 Receptor-Expressing Medium Spiny Neurons in the Nucleus Accumbens Shell

Kircher

Aziz

Mangieri

et al. 2018

Preprint

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Nucleus accumbens dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) have been implicated in the formation of dependence to many drugs of abuse including alcohol. Previous studies have revealed that acute alcohol exposure suppresses glutamatergic signaling within the accumbens and repeated alcohol exposure enhances glutamatergic signaling. D1-MSNs receive glutamatergic input from several brain regions and it is not currently known how individual inputs onto D1-MSNs are altered by alcohol experience. To Address this, we used virally mediated expression of Channelrhodopsin (ChR2) in ventral hippocampal (vHipp) glutamate neurons to selectively activate vHipp to D1-MSN synapses and compared synaptic adaptations in response to low and high alcohol experience in vitro and in vivo. Alcohol experience enhanced glutamatergic activity and abolished long-term depression (LTD) at ventral hippocampal (vHipp) to D1-MSN synapses. Following chronic alcohol experience GluA2lacking AMPA receptors, which are Ca-permeable, were inserted into vHipp to D1-MSN synapses. These alcohol-induced adaptations of glutamatergic signaling occurred at lower levels of exposure than previously reported. The loss of LTD expression and enhancement in glutamatergic signaling from the vHipp to D1-MSNs in the nucleus accumbens may play a critical role in the formation of alcohol dependence and enhancements in ethanol consumption. Reversal of alcohol-induced insertion of Ca-permeable AMPA receptors and enhancement of glutamatergic activity at vHipp to D1-MSNs presents potential targets for intervention during early exposure to alcohol. SIGNIFICANCE STATEMENTThe work presented here is the first to elucidate how an individual glutamatergic input onto D1-MSNs of the accumbens shell (shNAc) are altered by repeated ethanol exposure. Our findings suggest that glutamatergic input from the ventral hippocampus (vHipp) onto D1-MSNs is enhanced following drinking in a two-bottle choice (2BC) paradigm and is further enhanced by chronic intermittent ethanol (CIE) vapor exposure which escalated volitional ethanol intake.A critical finding was the insertion of Ca-permeable AMPA receptors into vHipp-shNAc D1-MSN synapses following CIE exposure, and more importantly following ethanol consumption in the absence of vapor exposure. These findings suggest that enhancements of glutamatergic input from the vHipp and insertion of Ca-permeable AMPARs play a role in the formation of ethanol dependence.

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Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior

Cannady

Rinker

Nimitvilai

et al. 2018

Handbook of Experimental Pharmacology

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Neural mechanisms underlying alcohol use disorder remain elusive, and this lack of understanding has slowed the development of efficacious treatment strategies for reducing relapse rates and prolonging abstinence. While synaptic adaptations produced by chronic alcohol exposure have been extensively characterized in a variety of brain regions, changes in intrinsic excitability of critical projection neurons are understudied. Accumulating evidence suggests that prolonged alcohol drinking and alcohol dependence produce plasticity of intrinsic excitability as measured by changes in evoked action potential firing and after-hyperpolarization amplitude. In this chapter, we describe functional changes in cell firing of projection neurons after long-term alcohol exposure that occur across species and in multiple brain regions. Adaptations in calcium-activated (K2), voltage-dependent (K7), and G protein-coupled inwardly rectifying (K3 or GIRK) potassium channels that regulate the evoked firing and after-hyperpolarization parallel functional changes in intrinsic excitability induced by chronic alcohol. Moreover, there are strong genetic links between alcohol-related behaviors and genes encoding K2, K7, and GIRK channels, and pharmacologically targeting these channels reduces alcohol consumption and alcohol-related behaviors. Together, these studies demonstrate that chronic alcohol drinking produces adaptations in K2, K7, and GIRK channels leading to impaired regulation of the after-hyperpolarization and aberrant cell firing. Correcting the deficit in the after-hyperpolarization with positive modulators of K2 and K7 channels and altering the GIRK channel binding pocket to block the access of alcohol represent a potentially highly effective pharmacological approach that can restore changes in intrinsic excitability and reduce alcohol consumption in affected individuals.

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Long‐term subregion‐specific encoding of enhanced ethanol intake by D1DR medium spiny neurons of the nucleus accumbens

Cited by 25 publications

References 48 publications

Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward

Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward

Ethanol Experience Enhances Glutamatergic Ventral Hippocampal Inputs to D1 Receptor-Expressing Medium Spiny Neurons in the Nucleus Accumbens Shell

Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior

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