Heroin Cue–Evoked Astrocytic Structural Plasticity at Nucleus Accumbens Synapses Inhibits Heroin Seeking

Kruyer, Anna; Scofield, Michael D.; Wood, D.J.; Reissner, Kathryn J.; Kalivas, Peter W.

doi:10.1016/j.biopsych.2019.06.026

Cited by 72 publications

(123 citation statements)

References 44 publications

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“…In the current study, we found that GLT-1 and GS but not GLAST were decreased in astrocyte after being induced into A1-like phenotype in vitro. In addition, METH withdrawal in vivo decreased expressions of both GLT-1 and GLAST in dCA1, which is consistent with previous findings about GLT-1 and GLAST in other drugs of models such as cocaine and heroin 27,30 . Taken together, these results indicate that the dysfunctions in astrocytic glutamate transporting system, especially GLT-1 might be key pathological molecules that contribute to the weakened capacity of astrocyte-drived Glu uptake by METH withdrawal.…”

Section: The Reduction Of Astrocyte-derived Glu Uptake Contribute To supporting

confidence: 92%

“…In the dCA1, the postsynaptic pyramidal neurons receive the glutamatergic afferents from dCA3, and astrocyte enwraps the pre-and post-neuronal components of synapse, which forming "tripartite synapse" 14,25 . Basal extrasynaptic Glu tone is maintained largely by presynaptic neuronal Glu release and astrocyte-mediated uptake of Glu 26,27 . Astrocytes undergo a dynamic shift between two different reactive states, A1 phenotype and A2 phenotype astrocytes.…”

Section: The Reduction Of Astrocyte-derived Glu Uptake Contribute To mentioning

confidence: 99%

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Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

Shi

et al. 2020

Preprint

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24Methamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could 25 induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive 26 deficits, but the synaptic etiology remains unclear. Here, we investigated the role of dCA1 tripartite 27 synapses and the potential therapeutic effects of electro-acupuncture (EA) in the METH withdrawal-28 induced spatial memory deficits. METH withdrawal weakened astrocytic capacity of Glu uptake, but 29 failed to change Glu release from dCA3, resulting in hyper-glutamatergic excitotoxicity at dCA1 30 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the 31 hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally 32 alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte 33 at tripartite synapses might be a novel target for developing therapeutic interventions against METH-34 associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for 35 the management of drugs-caused neurotoxicity.36 3

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Section: The Reduction Of Astrocyte-derived Glu Uptake Contribute To supporting

confidence: 92%

Section: The Reduction Of Astrocyte-derived Glu Uptake Contribute To mentioning

confidence: 99%

Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

Shi

et al. 2020

Preprint

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“…Recently, we found that heroin-associated cues rapidly and transiently increase the proximity of astroglial peripheral processes with the synapse (125) ( Figure 2D), and the transient reassociation of the astroglial surface with NA core synapses during heroin reinstatement appears to be compensatory. When the reassociation is prevented by knockdown of the actin binding protein ezrin, which is selectively expressed in PAPs (129), cue-induced heroin seeking was potentiated (125). Taken together, the enduring reductions in GLT-1 expression and changes in synaptic proximity of astrocyte processes after heroin extinction, along with their morphological plasticity during cue exposure, demonstrate a critical role for astrocytes in opioid seeking.…”

Section: Morphological Plasticitymentioning

confidence: 91%

The Opioid-Addicted Tetrapartite Synapse

Kruyer¹,

Chioma²,

Kalivas

2020

Biological Psychiatry

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Opioid administration in preclinical models induces long-lasting adaptations in reward and habit circuitry. The latest research demonstrates that in the nucleus accumbens, opioid-induced excitatory synaptic plasticity involves presynaptic and postsynaptic elements as well as adjacent astroglial processes and the perisynaptic extracellular matrix. We outline opioid-induced modifications within each component of the tetrapartite synapse and provide a neurobiological perspective on how these adaptations converge to produce addiction-related behaviors in rodent models. By incorporating changes observed at each of the excitatory synaptic compartments into a unified framework of opioid-induced glutamate dysregulation, we highlight new avenues for restoring synaptic homeostasis that might limit opioid craving and relapse vulnerability.

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“…Meanwhile, Lck‐GCaMP constructs have revealed the dynamics of astrocyte calcium signaling at the PAPs (Shigetomi et al., 2013; Shigetomi, Kracun, & Khakh, 2010). Recently, three‐dimensional reconstructions of Lck‐GFP‐transduced astrocytes were used to explore morphometric changes after administration of various drugs of abuse (Kruyer et al., 2019; Scofield et al., 2016; Siemsen et al., 2019; Testen et al., 2018) as well as for measurements of developmental changes (Testen et al., 2019).…”

Section: Commentarymentioning

confidence: 99%

“…In addition, immunohistochemistry (IHC) for synaptic markers such as synapsin‐1 and post‐synaptic density‐95 can be employed to assess synaptic colocalization of Lck‐GFP. Using these methods, our laboratory and others have shown changes in nucleus‐accumbens astrocytes associated with self‐administration of cocaine (Scofield et al., 2016; Testen et al., 2018), heroin (Kruyer, Scofield, Wood, Reissner, & Kalivas, 2019), and methamphetamine (Siemsen et al., 2019) as well as in other structures across development (Testen et al., 2019) and in response to severe stress (Jones, Paniccia, Lebonville, Reissner, & Lysle, 2018). The general methods employed in the above‐mentioned studies are described in the protocols below.…”

Section: Introductionmentioning

confidence: 99%

High‐Resolution Three‐Dimensional Imaging of Individual Astrocytes Using Confocal Microscopy

2020

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Astrocytes play numerous vital roles in the central nervous system. Accordingly, it is of merit to identify structural and functional properties of astrocytes in both health and disease. The majority of studies examining the morphology of astrocytes have employed immunoassays for markers such as glial fibrillary acidic protein, which are insufficient to encapsulate the considerable structural complexity of these cells. Herein, we describe a method utilizing a commercially available and validated, genetically encoded membrane‐associated fluorescent marker of astrocytes, AAV5‐GfaABC1D‐Lck‐GFP. This tool and approach allow for visualization of a single isolated astrocyte in its entirety, including fine peripheral processes. Astrocytes are imaged using confocal microscopy and reconstructed in three dimensions to obtain detailed morphometric data. We further provide an immunohistochemistry procedure to assess colocalization of isolated astrocytes with synaptic markers throughout the z‐plane. This technique, which can be utilized via a standard laboratory confocal microscope and Imaris software, allows for detailed analysis of the morphology and synaptic colocalization of astrocytes in fixed tissue. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Microinjection of AAV5‐GfaABC1D‐Lck‐GFP into the nucleus accumbens of rats Basic Protocol 2: Tissue processing and immunohistochemistry for post‐synaptic density‐95 Basic Protocol 3: Single‐cell image acquisition Basic Protocol 4: Three‐dimensional reconstruction of single cells Basic Protocol 5: Three‐dimensional colocalization analysis

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Heroin Cue–Evoked Astrocytic Structural Plasticity at Nucleus Accumbens Synapses Inhibits Heroin Seeking

Cited by 72 publications

References 44 publications

Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

The Opioid-Addicted Tetrapartite Synapse

High‐Resolution Three‐Dimensional Imaging of Individual Astrocytes Using Confocal Microscopy

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