D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons

Surmeier, D. James; Ding, Jun; Day, Michelle; Wang, Zhongfeng; Shen, Weisen

doi:10.1016/j.tins.2007.03.008

Cited by 996 publications

(960 citation statements)

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“…Though we were not in a position to address the identity of c-Fos-positive neurons in TLR4 -/-mice in the current study, we think these neurons may be D2-MSNs as activation of these neurons mainly controls aversive behaviors [37][38][39]. It is well-known that D2-MSNs are inhibited by DA [40], and xenobiotic activation of TLR4 results in an increase in DA in the NAc [20,33]. This may explain why TLR4 deficiency enhanced neuronal activity in the NAcSh after the novelty-seeking test.…”

Section: Discussionmentioning

confidence: 80%

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

Yan

Cheng

et al. 2016

Neurosci. Bull.

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Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine (DA) system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4 (TLR4), an important pattern-recognition receptor in the innate immune system, can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty-seeking and social interaction behaviors of TLR4-deficient (TLR4 -/-) and wild-type (WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed, large spaces. We found that TLR4 -/-mice exhibited reduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4 -/-mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approachavoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4 -/-mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly, the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell (NAcSh) in TLR4 -/-mice than in WT mice. Partially inactivating the NAcSh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4 -/-mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAcSh may contribute to this phenomenon.

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Section: Discussionmentioning

confidence: 80%

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

Yan

Cheng

et al. 2016

Neurosci. Bull.

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Section: Functional Evidencementioning

confidence: 99%

“…In addition, D2-class receptors modulate intracellular Ca2+ levels and a number of Ca2+-dependent intracellular signaling processes ( Figure 1A). Through diverse cAMP-and Ca2+-dependent and -independent mechanisms, DA influences neuronal activity, synaptic plasticity, and behavior [6][7][8][9]. Like most GPCRs, the responsiveness of DA receptors is primarily controlled by the classical β arrestin-and GPCR kinase (GRK)-regulated desensitization process ( Figure 1B) [10].…”

mentioning

confidence: 99%

“…We restrict our focus to electrophysiological studies in which synaptically evoked events were analyzed and dopaminergic actions could be carefully attributed to the postsynaptic site. For detailed reviews of DA modulation of receptor activity, neuronal excitability, and synaptic function, see [6][7][8][9].DA modulation of postsynaptic responses-Brief bath application of low concentrations of D1-class agonists led to delayed onset and prolonged potentiation of NMDAR-mediated excitatory postsynaptic current (EPSC) in layer V PFC neurons. This potentiation was attributed to activation of postsynaptic D1-class receptors [54] and is consistent with the involvement of postsynaptic cAMP signaling [7].…”

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confidence: 99%

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Dopaminergic signaling in dendritic spines

Yao

Spealman

Zhang

2008

Biochemical Pharmacology

108

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Dopamine regulates movement, motivation, reward, and learning and is implicated in numerous neuropsychiatric and neurological disorders. The action of dopamine is mediated by a family of seven-transmembrane G protein-coupled receptors encoded by at least five dopamine receptor genes (D1, D2, D3, D4, and D5), some of which are major molecular targets for diverse neuropsychiatric medications. Dopamine receptors are present throughout the soma and dendrites of the neuron, but accumulating ultrastructural and biochemical evidence indicates that they are concentrated in dendritic spines, where most of the glutamatergic synapses are established. By modulating local channels, receptors, and signaling modules in spines, this unique population of postsynaptic receptors is strategically positioned to control the excitability and synaptic properties of spines and mediate both the tonic and phasic aspects of dopaminergic signaling with remarkable precision and versatility. The molecular mechanisms that underlie the trafficking, targeting, anchorage, and signaling of dopamine receptors in spines are, however, largely unknown. The present commentary focuses on this important subpopulation of postsynaptic dopamine receptors with emphases on recent molecular, biochemical, pharmacological, ultrastructural, and physiological studies that provide new insights about their regulatory mechanisms and unique roles in dopamine signaling. The Central Dopaminergic Systems: An OverviewDopamine (DA) is a prototypical slow neurotransmitter that plays pivotal roles in a variety of cognitive, motivational, neuroendocrine, and motor functions [1][2]. Two major groups of DAcontaining neurons in the mammalian brain reside in the substantia nigra pars compacta (SN) and the ventral tegmental area (VTA) [3]. SN neurons form the nigrostriatal pathway, which projects mainly to the dorsal part of striatum where they control postural reflexes and initiation of movements. VTA neurons give rise to two pathways: the mesolimbic pathway, which projects to the subcortical and limbic nuclei, and the mesocortical pathway, which projects mainly to the cingulate, entorhinal and medial prefrontal cortices. Dysfunction of dopaminergic transmission in these major pathways has been implicated in an array of neurological and neuropsychiatric disorders, including Parkinson's disease, Huntington's diseases, schizophrenia, attention-deficit hyperactivity disorder (ADHD), and drug addiction [1][2]. Drugs targeting dopaminergic mechanisms are widely used to manage these and other conditions.The action of DA is mediated by a family of seven-transmembrane G protein-coupled receptors (GPCRs) encoded by at least five DA receptor genes (D1, D2, D3, D4, and D5) in the mammalian brain [4]. These receptors are classified into two subfamilies, the D1-class and Corresponding author: Wei-Dong Yao, Ph.D., Department of Psychiatry, Harvard Medical School, Beth Israel Deaconess Medical Center, New England Primate Research Center, One Pine Hill Drive, P.O. Box 9102, Southborough,...

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“…Despite these difficulties, recently developed bacterial artificial chromosome (BAC) transgenic mice expressing enhanced green fluorescent protein (EGFP) enable the examination of gene expression in these two distinct striatal neurons (Durieux et al, 2011;Ena et al, 2011;Gong et al, 2003;Surmeier et al, 2007). Morphologically indistinguishable striatopallidal and striatonigral neuronal subtypes comprise approximately 90-95% of striatal neurons (Graybiel, 2000;Humphries and Prescott, 2010).…”

Section: Introductionmentioning

confidence: 99%

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Nam

Bruner

Choi

2013

Molecules and Cells

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Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.

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D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons

Cited by 996 publications

References 86 publications

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

Dopaminergic signaling in dendritic spines

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

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