Homeostatic Synapse-Driven Membrane Plasticity in Nucleus Accumbens Neurons

Ishikawa, Masago; Mu, Ping; Moyer, Jason T.; Wolf, John A.; Quock, Raymond M.; Davies, Neal M.; Hu, Xiu‐Ti; Schlüter, Oliver M.; Dong, Yan

doi:10.1523/jneurosci.5703-08.2009

Cited by 106 publications

(147 citation statements)

References 57 publications

(87 reference statements)

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“…However, studies show that coactivation of D1-like and D2-like receptors using DA or DAR agonists enhances MSNs firing in the NAcSh [35], which is opposite to what we have observed using cocaine in our previous and present studies [12,16,19,20,29] and by other groups [19,20,29] (reviewed in [13]). Altogether, these studies suggest that cocaine-induced FRD in NAcSh D1R-MSNs may involve additional or different mechanisms from DA signaling.…”

Section: Cocaine Decreases Nacsh Neuronal Intrinsic Excitability In Dcontrasting

confidence: 99%

“…1a), consistent with previous studies that were performed in similar conditions, that is, without distinguishing MSN subtypes [DA 1 vs. DA 2 receptorexpressing MSNs, (D1R-and D2R-MSNs)] ( [16,[18][19][20], reviewed in [13]). To determine its cellular mechanism, we developed a freshly dissected brain slice preparation that mimics in vivo physiological conditions.…”

Section: Cocaine Decreases Nacsh Neuronal Intrinsic Excitability In Dsupporting

confidence: 90%

“…Although cocaine-induced FRD is specific to D1R-MSNs, both our previous and others' studies reliably obtained cocaine-induced FRD without distinguishing the two sub-populations of MSNs ( [11,12,16,[18][19][20], reviewed in [13]). Although this may appear surprising, it is reminiscent of cocaine-induced synaptic potentiation in NAcSh neurons, that is, cocaine-induced synaptic plasticity in the NAcSh is specific to D1R-MSNs ( [28], reviewed in [30]) but it is also obtained without distinguishing the two sub-populations of MSNs ( [15], reviewed in [31,32]).…”

Section: Cocaine Decreases Nacsh Neuronal Intrinsic Excitability In Dmentioning

confidence: 49%

“…3a). Cocaine is an agonist of σ1 [3] (reviewed in [37]) and has been shown to alter several sodium, calcium and potassium conductances in NAc MSNs, each of which is consistent with a decrease in depolarizationinduced firing [18,19,[48][49][50]. These data raise the hypothesis that cocaine binding to σ1 is the initial event that leads to the regulation of VGICs responsible for the FRD in NAcSh D1R-MSNs.…”

Section: Cocaine Decreases Nacsh Neuronal Intrinsic Excitability In Dmentioning

confidence: 83%

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Cocaine engages a non-canonical, dopamine-independent, mechanism that controls neuronal excitability in the nucleus accumbens

et al. 2018

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Drug-induced enhanced dopamine (DA) signaling in the brain is a canonical mechanism that initiates addiction processes. However, indirect evidence suggests that cocaine also triggers non-canonical, DA-independent, mechanisms that contribute to behavioral responses to cocaine, including psychomotor sensitization and cocaine self-administration. Identifying these mechanisms and determining how they are initiated is fundamental to further our understanding of addiction processes. Using physiologically relevant in vitro tractable models, we found that cocaine-induced hypoactivity of nucleus accumbens shell (NAcSh) medium spiny neurons (MSNs), one hallmark of cocaine addiction, is independent of DA signaling. Combining brain slice studies and site-directed mutagenesis in HEK293T cells, we found that cocaine binding to intracellular sigma-1 receptor (σ1) initiates this mechanism. Subsequently, σ1 binds to Kv1.2 potassium channels, followed by accumulation of Kv1.2 in the plasma membrane, thereby depressing NAcSh MSNs firing. This mechanism is specific to D1 receptor-expressing MSNs. Our study uncovers a mechanism for cocaine that bypasses DA signaling and leads to addiction-relevant neuroadaptations, thereby providing combinatorial strategies for treating stimulant abuse.

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Section: Cocaine Decreases Nacsh Neuronal Intrinsic Excitability In Dcontrasting

confidence: 99%

Section: Cocaine Decreases Nacsh Neuronal Intrinsic Excitability In Dsupporting

confidence: 90%

Section: Cocaine Decreases Nacsh Neuronal Intrinsic Excitability In Dmentioning

confidence: 49%

Section: Cocaine Decreases Nacsh Neuronal Intrinsic Excitability In Dmentioning

confidence: 83%

See 2 more Smart Citations

Cocaine engages a non-canonical, dopamine-independent, mechanism that controls neuronal excitability in the nucleus accumbens

et al. 2018

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“…In addition to the microdialysis studies mentioned above, which showed changes in nonsynaptic glutamate pools, other results suggested decreased activity of glutamatergic afferents to the nucleus accumbens during cocaine withdrawal (Hammer and Cooke 1994;Goldstein and Volkow 2002;Sun and Rebec 2006;Porrino et al 2007). In addition, electrophysiological studies showed that repeated cocaine exposure decreased the intrinsic excitability of accumbens neurons by altering voltage-gated conductances (Zhang et al 1998(Zhang et al , 2002Hu et al 2004Hu et al , 2005Dong et al 2006;Ishikawa et al 2009;Kourrich and Thomas 2009;Mu et al 2010). Each of these three adaptations-decreased nonsynaptic glutamate, decreased activity of glutamatergic afferents, and decreased intrinsic excitability-has the potential to result in a compensatory increase in glutamate receptor expression in the accumbens (for a critical evaluation of the role of each adaptation see Wolf 2010a).…”

Section: Chronic Cocaine Synaptic and Nonsynaptic Glutamate And Ampmentioning

confidence: 99%

Psychostimulant-Induced Neuroadaptations in Nucleus Accumbens AMPA Receptor Transmission

Pierce

Wolf

2012

Cold Spring Harbor Perspectives in Medicine

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Medium spiny neurons of the nucleus accumbens serve as the interface between corticolimbic regions that elicit and modulate motivated behaviors, including those related to drugs of abuse, and motor regions responsible for their execution. Medium spiny neurons are excited primarily by AMPA-type glutamate receptors, making AMPA receptor transmission in the accumbens a key regulatory point for addictive behaviors. In animal models of cocaine addiction, changes in the strength of AMPA receptor transmission onto accumbens medium spiny neurons have been shown to underlie cocaine-induced behavioral adaptations related to cocaine seeking. Here we review changes in AMPA receptor levels and subunit composition that occur after discontinuing different types of cocaine exposure, as well as changes elicited by cocaine reexposure following abstinence or extinction. Signaling pathways that regulate these cocaine-induced adaptations will also be considered, as they represent potential targets for addiction pharmacotherapies.F unctionally relevant changes in nucleus accumbens glutamatergic transmission induced by psychostimulants (i.e., amphetamine or cocaine) were first identified in the 1990s following two scientific advances: (1) the development of relatively selective AMPA/kainate and NMDA receptor antagonists (Wong et al. 1986;Honore et al. 1988), and (2) a greater appreciation of the influence of glutamatergic afferents to the nucleus accumbens (Albin et al. 1989;Alexander et al. 1990). Studies on the effects of psychostimulants on glutamate transmission were also driven by the realization that the regulated trafficking of glutamate receptors in and out of synapses is a major contributor to changes in synaptic strength during hippocampal synaptic plasticity (Malinow and Malenka 2002).Early studies of glutamate's role in psychostimulant addiction focused primarily on a form of psychostimulant-induced neuronal and behavioral plasticity known as behavioral sensitization wherein repeated exposure to psychostimulants (usually in the form of experimenterdelivered injections) results in a progressive and enduring enhancement of psychostimulant-induced behavioral responses. By the early 1990s,

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Potentiation of synaptic strength and intrinsic excitability in the nucleus accumbens after 10 days of morphine withdrawal

Shi

Wei

et al. 2012

J of Neuroscience Research

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Neuroadaptations in the nucleus accumbens (NAc) are associated with the development of drug addiction. Plasticity in synaptic strength and intrinsic excitability of NAc medium spiny neurons (MSNs) play critical roles in addiction induced by different classes of abused drugs. However, it is unknown whether morphine exposure influences synaptic strength, intrinsic excitability or both in NAc. Here we show that chronic withdrawal (10 days after the last injection) from repeated morphine exposure elicited potentiation in both glutamatergic synaptic strength and intrinsic excitability of MSNs in NAc shell (NAcSh). The potentiation of synaptic strength was demonstrated by an increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs), a decrease in the paired-pulse ratio (PPR), and an increase in the ratio of α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR)- to N-methyl-D-aspartate receptors (NMDAR)-mediated currents. The potentiation of intrinsic excitability was mediated by inhibition of the sustained potassium currents via extrasynaptic NMDAR activation. The function of the presynaptic group II metabotropic glutamate receptors (mGluR2/3) was downregulated, enhancing the probability of glutamate release on synaptic terminals during chronic morphine withdrawal. Pretreatment with the mGluR2/3 agonist LY379268 completely blocked potentiation of both synaptic strength and intrinsic excitability. These results suggest that chronic morphine withdrawal downregulates mGluR2/3 to induce potentiation of MSN glutamatergic synapse via increased glutamate release, leading to potentiation of intrinsic excitability. Such potentiation of both synaptic strength and intrinsic excitability might contribute to neuroadaptations induced by morphine application.

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Homeostatic Synapse-Driven Membrane Plasticity in Nucleus Accumbens Neurons

Cited by 106 publications

References 57 publications

Cocaine engages a non-canonical, dopamine-independent, mechanism that controls neuronal excitability in the nucleus accumbens

Cocaine engages a non-canonical, dopamine-independent, mechanism that controls neuronal excitability in the nucleus accumbens

Psychostimulant-Induced Neuroadaptations in Nucleus Accumbens AMPA Receptor Transmission

Potentiation of synaptic strength and intrinsic excitability in the nucleus accumbens after 10 days of morphine withdrawal

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