Cocaine Triggers Astrocyte-Mediated Synaptogenesis

Wang, Junshi; Li, King-Lun; Shukla, Avani; Beroun, Anna; Ishikawa, Masago; Huang, Xiaojie; Wang, Yao; Yang, Yongchang; Bastola, Noah D.; Huang, Hsin Hui; Kramer, Lily E.; Chao, Terry; Huang, Yanhua H.; Sesack, Susan R.; Nestler, Eric J.; Schlüter, Oliver M.; Dong, Yan

doi:10.1016/j.biopsych.2020.08.012

Cited by 58 publications

(41 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These adaptations are typically long-lasting and often differ substantially among drugs of different classes. For example, synapse formation versus elimination is induced in NAc MSNs after withdrawal from cocaine versus morphine, respectively (6,7). Focusing on extinction and reinstatement of heroin seeking after withdrawal from heroin self-administration, the current study demonstrates a 'transient' form of synaptic plasticity in NAc MSNs.…”

mentioning

confidence: 74%

A Third-Party Facilitator of Bipartisanship

Zinsmaier

Dong

2021

Biological Psychiatry

Self Cite

View full text Add to dashboard Cite

Often times, biological processes are reminiscent of a two-party system, wherein two differential or opposing forces must coordinate to achieve a balanced output, and drug addiction is no exception. In the nucleus accumbens (NAc), the two parties in play are D1 and D2 dopamine receptor-expressing medium spiny neurons (MSNs). Differentially embedded in NAc circuits, D1 and D2 MSNs regulate different aspects of motivated behaviors related to drug addiction, very often, in an opposing manner (1). To form coherent and reliable behavioral outputs, e.g., persistent cue-induced drug seeking, cooperative, as opposed to individualistic, adaptations between these two neuronal types is required. However, as we've witnessed with many two-party systems, reaching any sort of bipartisan deal is difficult when left to the two insiders.

show abstract

mentioning

confidence: 74%

A Third-Party Facilitator of Bipartisanship

Zinsmaier

Dong

2021

Biological Psychiatry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Redundancy between components of this complex signaling network is exemplified by the observation that selective inhibition of the transcription factors Elk1 ( Besnard et al, 2011 ) or CREB ( Brown et al, 2011 ), which are activated downstream from the ERK pathway, fully blocks cocaine-evoked increase in MSN dendritic spine density. Extracellular matrix proteins and cell–cell adhesion also play an essential role in cocaine-induced increase in spine density, notably through integrins ( Chen et al, 2008 ; Wiggins et al, 2009 ; Kerrisk and Koleske, 2013 ), SynCAM1 ( Giza et al, 2013 ), or thrombospondin ( Wang et al, 2021 ).…”

Section: Drug-evoked Morphological Changes In Medium-sized Spiny Neurons Subtypes and Regulation Of Synaptogenesismentioning

confidence: 99%

“…Hence, while a first cocaine injection would create more dendritic spines and potentiate glutamatergic transmission, repeated injection would induce new spines hosting silent synapses that would become active upon deprivation (Boudreau et al, 2007;Graziane et al, 2016). Along those lines, some studies reported that chronic cocaine increases the percentage of spines with small size, which is compatible with an increase of AMPAR-lacking silent synapses (LaPlant et al, 2010;Dietz et al, 2012;Cahill et al, 2016;Wang et al, 2021), whereas an enhancement of dendritic spine heads has been reporter after a protracted withdrawal from cocaine (Graziane et al, 2016). By contrast, other studies reported either no changes (Dumitriu et al, 2012;Heck et al, 2015) or an increase (Dobi et al, 2011) in spine size 1 or 2 days after the last cocaine injection.…”

Section: Drug-evoked Morphological Changes In Medium-sized Spiny Neurons Subtypes and Regulation Of Synaptogenesismentioning

confidence: 99%

Cell-Type-Specific Adaptions in Striatal Medium-Sized Spiny Neurons and Their Roles in Behavioral Responses to Drugs of Abuse

Allichon

Ortiz

Pousinha

et al. 2021

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

Drug addiction is defined as a compulsive pattern of drug-seeking- and taking- behavior, with recurrent episodes of abstinence and relapse, and a loss of control despite negative consequences. Addictive drugs promote reinforcement by increasing dopamine in the mesocorticolimbic system, which alters excitatory glutamate transmission within the reward circuitry, thereby hijacking reward processing. Within the reward circuitry, the striatum is a key target structure of drugs of abuse since it is at the crossroad of converging glutamate inputs from limbic, thalamic and cortical regions, encoding components of drug-associated stimuli and environment, and dopamine that mediates reward prediction error and incentive values. These signals are integrated by medium-sized spiny neurons (MSN), which receive glutamate and dopamine axons converging onto their dendritic spines. MSN primarily form two mostly distinct populations based on the expression of either DA-D1 (D1R) or DA-D2 (D2R) receptors. While a classical view is that the two MSN populations act in parallel, playing antagonistic functional roles, the picture seems much more complex. Herein, we review recent studies, based on the use of cell-type-specific manipulations, demonstrating that dopamine differentially modulates dendritic spine density and synapse formation, as well as glutamate transmission, at specific inputs projecting onto D1R-MSN and D2R-MSN to shape persistent pathological behavioral in response to drugs of abuse. We also discuss the identification of distinct molecular events underlying the detrimental interplay between dopamine and glutamate signaling in D1R-MSN and D2R-MSN and highlight the relevance of such cell-type-specific molecular studies for the development of innovative strategies with potential therapeutic value for addiction. Because drug addiction is highly prevalent in patients with other psychiatric disorders when compared to the general population, we last discuss the hypothesis that shared cellular and molecular adaptations within common circuits could explain the co-occurrence of addiction and depression. We will therefore conclude this review by examining how the nucleus accumbens (NAc) could constitute a key interface between addiction and depression.

show abstract

“…In addition, cocaine-induced abnormal behaviors such as drug seeking and relapse after withdrawal are mediated by aberrant Ca 2+ signals in astrocytes in the nucleus accumbens shell (NAcSh). The administration of cocaine increases aberrant Ca 2+ signals in NAcSh astrocytes, which stimulates the production of the synaptogenic molecule TSP-2, leading to the activation of its receptor a2d-1 and the generation of AMPA receptor-silent glutamatergic synapses [ 25 ]. Importantly, the cocaine-evoked formation of glutamatergic silent synapses in NacSh functions as a memory trace of cocaine experience, and thus, the aberrant Ca 2+ signals in astrocytes could be a cause also of cue-associated memory traces that promote cocaine relapse.…”

Section: Other Brain Diseases and Aberrant Astrocytic Ca 2+ -Mediated Synapse Remodelingmentioning

confidence: 99%

Abnormal Ca2+ Signals in Reactive Astrocytes as a Common Cause of Brain Diseases

Koizumi

Shigetomi

Sano

et al. 2021

IJMS

View full text Add to dashboard Cite

In pathological brain conditions, glial cells become reactive and show a variety of responses. We examined Ca2+ signals in pathological brains and found that reactive astrocytes share abnormal Ca2+ signals, even in different types of diseases. In a neuropathic pain model, astrocytes in the primary sensory cortex became reactive and showed frequent Ca2+ signals, resulting in the production of synaptogenic molecules, which led to misconnections of tactile and pain networks in the sensory cortex, thus causing neuropathic pain. In an epileptogenic model, hippocampal astrocytes also became reactive and showed frequent Ca2+ signals. In an Alexander disease (AxD) model, hGFAP-R239H knock-in mice showed accumulation of Rosenthal fibers, a typical pathological marker of AxD, and excessively large Ca2+ signals. Because the abnormal astrocytic Ca2+ signals observed in the above three disease models are dependent on type II inositol 1,4,5-trisphosphate receptors (IP3RII), we reanalyzed these pathological events using IP3RII-deficient mice and found that all abnormal Ca2+ signals and pathologies were markedly reduced. These findings indicate that abnormal Ca2+ signaling is not only a consequence but may also be greatly involved in the cause of these diseases. Abnormal Ca2+ signals in reactive astrocytes may represent an underlying pathology common to multiple diseases.

show abstract

Cocaine Triggers Astrocyte-Mediated Synaptogenesis

Cited by 58 publications

References 93 publications

A Third-Party Facilitator of Bipartisanship

A Third-Party Facilitator of Bipartisanship

Cell-Type-Specific Adaptions in Striatal Medium-Sized Spiny Neurons and Their Roles in Behavioral Responses to Drugs of Abuse

Abnormal Ca2+ Signals in Reactive Astrocytes as a Common Cause of Brain Diseases

Contact Info

Product

Resources

About