4R Tau Modulates Cocaine-Associated Memory through Adult Dorsal Hippocampal Neurogenesis

Li, Hongchun; Xu, Wei; Wang, Denian; Wang, Liang; Fang, Qiyao; Wan, Xuemei; Zhang, Jiamei; Hu, Y.; Li, Huifang; Zhang, Jie; Liu, Chunqi; Liu, Xiaocong; Wang, Yonghai; Liu, Bin; Hu, Zhengtao; Zhao, Ying; Bu, Qian; Wang, Hongbo; Tian, Jingwei; Zhao, Yinglan; Cen, Xiaobo

doi:10.1523/jneurosci.2848-20.2021

Cited by 8 publications

(9 citation statements)

References 54 publications

(63 reference statements)

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“…In the present study, we explored the mechanism by which Fyn mediates cocaine-associated memory formation. We found that cocaine exposure increases Fyn activity in the hippocampus and that Fyn may regulate Tau expression, which plays an important role in cocaineassociated memory formation (Li et al, 2021). Our results suggested that inactivation of the Src kinase Fyn in the hippocampus significantly disrupts cocaine-induced seeking behaviours in a self-administration paradigm and a cocaine-CPP paradigm without altering locomotor activity.…”

Section: Discussionmentioning

confidence: 57%

“…Tau, a microtubule-associated scaffolding protein, was shown to be necessary for drug-associated memory formation in our previous study (Li et al, 2021). In our previous research, we first found that Tau expression is significantly downregulated in the hippocampus during cocaine-associated memory formation, promoting adult hippocampal neurogenesis in the hippocampal dentate gyrus and facilitating enhanced cocaineassociated memory formation (Li et al, 2021). Nevertheless, the mechanism underlying the reduction in Tau levels during cocaine-associated memory formation remains unclear.…”

Section: Introductionmentioning

confidence: 98%

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The Src-Kinase Fyn is Required for Cocaine-Associated Memory Through Regulation of Tau

Zhou

Chen

et al. 2022

Front. Pharmacol.

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Drug-associated context-induced relapse of cocaine-seeking behaviour requires the retrieval of drug-associated memory. Studies exploring the underlying neurobiological mechanism of drug memory formation will likely contribute to the development of treatments for drug addiction and the prevention of relapse. In our study, we applied a cocaine-conditioned place preference (CPP) paradigm and a self-administration paradigm (two drug-associated memory formation model) to confirm the hypothesis that the Src kinase Fyn critically regulates cocaine-associated memory formation in the hippocampus. For this experiment, we administered the Src kinase inhibitor PP2 into the bilateral hippocampus before cocaine-CPP and self-administration training, and the results showed that pharmacological manipulation of the Src kinase Fyn activity significantly attenuated the response to cocaine-paired cues in the cocaine-CPP and self-administration paradigms, indicating that hippocampal Fyn activity contributes to cocaine-associated memory formation. In addition, the regulation of cocaine-associated memory formation by Fyn depends on Tau expression, as restoring Tau to normal levels disrupted cocaine memory formation. Together, these results indicate that hippocampal Fyn activity plays a key role in the formation of cocaine-associated memory, which underlies cocaine-associated contextual stimulus-mediated regulation of cocaine-seeking behaviour, suggesting that Fyn represents a promising therapeutic target for weakening cocaine-related memory and treating cocaine addiction.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 98%

The Src-Kinase Fyn is Required for Cocaine-Associated Memory Through Regulation of Tau

Zhou

Chen

et al. 2022

Front. Pharmacol.

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“…However, the changes in MAPs expression during learning and memory do not always comprise more protein synthesis, as opposite changes have also been found [162]. For instance, both Tau long isoforms expression and Tau-dependent P13K signaling are decreased during cocaine-associated memory formation, which was abolished by Tau overexpression [162]; when extinction is achieved in this paradigm, Tau long isoforms return to basal levels [162]. It is possible that learning-dependent expression changes in these Tau isoforms drive the dynamic state of neuronal MTs [163].…”

Section: Microtubular Reconfiguration During Brain Functionmentioning

confidence: 99%

“…Memory consolidation is accompanied by increased expression of MAP2 and β-tubulin [155][156][157][158], which is reflected in increased MAP2 immunohistochemical staining [159][160][161]. However, the changes in MAPs expression during learning and memory do not always comprise more protein synthesis, as opposite changes have also been found [162]. For instance, both Tau long isoforms expression and Tau-dependent P13K signaling are decreased during cocaine-associated memory formation, which was abolished by Tau overexpression [162]; when extinction is achieved in this paradigm, Tau long isoforms return to basal levels [162].…”

Section: Microtubular Reconfiguration During Brain Functionmentioning

confidence: 99%

Microtubules as Regulators of Neural Network Shape and Function: Focus on Excitability, Plasticity and Memory

Peña‐Ortega

Robles-Gómez

Xolalpa-Cueva

2022

Cells

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Neuronal microtubules (MTs) are complex cytoskeletal protein arrays that undergo activity-dependent changes in their structure and function as a response to physiological demands throughout the lifespan of neurons. Many factors shape the allostatic dynamics of MTs and tubulin dimers in the cytosolic microenvironment, such as protein–protein interactions and activity-dependent shifts in these interactions that are responsible for their plastic capabilities. Recently, several findings have reinforced the role of MTs in behavioral and cognitive processes in normal and pathological conditions. In this review, we summarize the bidirectional relationships between MTs dynamics, neuronal processes, and brain and behavioral states. The outcomes of manipulating the dynamicity of MTs by genetic or pharmacological approaches on neuronal morphology, intrinsic and synaptic excitability, the state of the network, and behaviors are heterogeneous. We discuss the critical position of MTs as responders and adaptative elements of basic neuronal function whose impact on brain function is not fully understood, and we highlight the dilemma of artificially modulating MT dynamics for therapeutic purposes.

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“…GSK-3β is involved in the development of behavioral sensitization to the locomotor activating effects of cocaine in rats [ 190 ], and cocaine withdrawal disrupts the circadian regulation of GSK-3β [ 191 ]. Knockout of Tau enhances cocaine conditioned place preference in mice while Tau overexpression in the hippocampus suppresses cocaine conditioned place preference [ 192 ]. The identification of parallel pathways for the regulation of psychostimulant response in flies and mammals has implications for the identification of novel regulators of psychostimulant response.…”

Section: Studying Psychostimulant Abuse With Drosophilamentioning

confidence: 99%

The Use of Drosophila to Understand Psychostimulant Responses

2022

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The addictive properties of psychostimulants such as cocaine, amphetamine, methamphetamine, and methylphenidate are based on their ability to increase dopaminergic neurotransmission in the reward system. While cocaine and methamphetamine are predominately used recreationally, amphetamine and methylphenidate also work as effective therapeutics to treat symptoms of disorders including attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Although both the addictive properties of psychostimulant drugs and their therapeutic efficacy are influenced by genetic variation, very few genes that regulate these processes in humans have been identified. This is largely due to population heterogeneity which entails a requirement for large samples. Drosophila melanogaster exhibits similar psychostimulant responses to humans, a high degree of gene conservation, and allow performance of behavioral assays in a large population. Additionally, amphetamine and methylphenidate reduce impairments in fly models of ADHD-like behavior. Therefore, Drosophila represents an ideal translational model organism to tackle the genetic components underlying the effects of psychostimulants. Here, we break down the many assays that reliably quantify the effects of cocaine, amphetamine, methamphetamine, and methylphenidate in Drosophila. We also discuss how Drosophila is an efficient and cost-effective model organism for identifying novel candidate genes and molecular mechanisms involved in the behavioral responses to psychostimulant drugs.

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4R Tau Modulates Cocaine-Associated Memory through Adult Dorsal Hippocampal Neurogenesis

Cited by 8 publications

References 54 publications

The Src-Kinase Fyn is Required for Cocaine-Associated Memory Through Regulation of Tau

The Src-Kinase Fyn is Required for Cocaine-Associated Memory Through Regulation of Tau

Microtubules as Regulators of Neural Network Shape and Function: Focus on Excitability, Plasticity and Memory

The Use of Drosophila to Understand Psychostimulant Responses

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