The cAMP-response-element-binding protein interacts, but Fos protein does not interact, with the proenkephalin enhancer in rat striatum.

Konradi, Christine; Kobierski, Linda A.; Nguyen, Tri Minh; Heckers, Stephan; Hyman, Steven E.

doi:10.1073/pnas.90.15.7005

Cited by 132 publications

(103 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high density of G-protein coupled receptors, many of which are coupled to adenylyl cyclase, attracts attention to the role and function of cyclic AMP-mediated gene expression in striatal neurons. The proenkephalin gene is a perfect candidate to study cyclic AMP-mediated gene expression in the striatum, as it codes for a neuromodulator with documented functions, is located in the striatum, and is sensitive to changes in cyclic AMP levels [4,5,14,15]. Among the G-protein coupled receptors in the striatum are dopamine and adenosine receptors, both of which regulate levels of proenkephalin mRNA and enkephalin protein [12,14,15,17,20].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Striatal proenkephalin gene induction: coordinated regulation by cyclic AMP and calcium pathways

Konradi

Macı́as

Dudman

et al. 2003

Molecular Brain Research

Self Cite

View full text Add to dashboard Cite

Enkephalin modulates striatal function, thereby affecting motor performance and addictive behaviors. The proenkephalin gene is also used as a model to study cyclic AMP-mediated gene expression in striatal neurons. The second messenger pathway leading to proenkephalin expression demonstrates how cyclic AMP pathways are synchronized with depolarization. We show that cyclic AMP-mediated regulation of the proenkephalin gene is dependent on the activity of L-type Ca 2+ channels. Inhibition of L-type Ca 2+ channels blocks forskolin-mediated induction of proenkephalin. The Ca 2+ -activated kinase, Ca 2+ /calmodulin kinase, as well as the cyclic AMPactivated kinase, protein kinase A (PKA), are both necessary for the induction of the proenkephalin promoter. Similarly, both kinases are needed for the L-type Ca 2+ channel-mediated induction of proenkephalin. This synchronization of second messenger pathways provides a coincidence mechanism that gates proenkephalin synthesis in striatal neurons, ensuring that levels are increased only in the presence of activated PKA and depolarization.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The transcription factor CREB has been shown to be involved in forskolin-mediated induction of the proenkephalin gene [14,15]. The inhibitory potential of KN62 on CREB phosphorylation by glutamate, NMDA, KCl and FPL 64176 was determined in dose-response curves.…”

Section: Determination Of Kinase Inhibitor Concentrationmentioning

confidence: 99%

Striatal proenkephalin gene induction: coordinated regulation by cyclic AMP and calcium pathways

Konradi

Macı́as

Dudman

et al. 2003

Molecular Brain Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…SCH23990 was the only antagonist, however, that impaired performance after the task had been well-learned, indicating at least a dual role for dopamine in the striatum for both associative and motor functions. Indeed, there is much evidence implicating striatal dopamine in both cellular plasticity (Konradi et al 1993;Cepeda and Levine 1998;Floresco et al 2001;Thomas and Malenka 2003) and behavioral activation (Fibiger et al 1976;Salamone 1987;Floresco et al 1996). Thus, it is possible that under these circumstances both D1 and AMPA/KA receptors could be used to guide proper behavioral set switching early in learning (Koob et al 1978;Gelissen and Cools 1988;Bakshi and Kelley 1991;van den Bos et al 1991;Baldo et al 2002).…”

Section: D1 Receptor Activation Within the Nucleus Accumbens Regulatementioning

confidence: 99%

AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: A context-limited role in the encoding and consolidation of instrumental memory

Hernandez¹,

Andrzejewski²,

Sadeghian³

et al. 2005

Learn. Mem.

View full text Add to dashboard Cite

Neural integration of glutamate-and dopamine-coded signals within the nucleus accumbens (NAc) is a fundamental process governing cellular plasticity underlying reward-related learning. Intra-NAc core blockade of NMDA or D1 receptors in rats impairs instrumental learning (lever-pressing for sugar pellets), but it is not known during which phase of learning (acquisition or consolidation) these receptors are recruited, nor is it known what role AMPA/kainate receptors have in these processes. Here we show that pre-trial intra-NAc core administration of the NMDA, AMPA/KA, and D1 receptor antagonists AP-5 (1 µg/0.5 µL), LY293558 (0.01 or 0.1 µg/0.5 µL), and SCH23390 (1 µg/0.5 µL), respectively, impaired acquisition of a lever-pressing response, whereas post-trial administration left memory consolidation unaffected. An analysis of the microstructure of behavior while rats were under the influence of these drugs revealed that glutamatergic and dopaminergic signals contribute differentially to critical aspects of the initial, randomly emitted behaviors that enable reinforcement learning. Thus, glutamate and dopamine receptors are activated in a time-limited fashion-only being required while the animals are actively engaged in the learning context.In order to survive in changing environments, animals must be able to acquire, consolidate, and retrieve pertinent information regarding a given stimulus situation. The ability to learn associations between various stimuli and events, including motor actions, is the basis of instrumental learning (Rescorla 1991;Dickinson and Balleine 1994). Appetitive instrumental learning occurs when an animal associates its behavior with a favorable outcome such as food, sex, or the avoidance of pain. For instance, in a common experimental model of instrumental learning, a hungry rat learns to press a lever to obtain a food reward.The nucleus accumbens (NAc) and its associated circuitry have been linked to the acquisition of adaptive motor responses and the control of behaviors related to natural reinforcers (Setlow 1997;Parkinson et al. 2000;Corbit et al. 2001). Because of the rich glutamatergic and dopaminergic innervation of the NAc from regions associated with motivational, cognitive, and sensory processes, many studies have focused on the role of these neurotransmitter systems with respect to instrumental and incentive learning (Berridge and Robinson 1998;Cardinal et al. 2002;Beninger and Gerdjikov 2004;Kelley 2004). For example, blockade of glutamate (N-methyl-D-aspartate, NMDA) or dopamine D1 receptors within the NAc core potently impairs instrumental learning, and coinfusion of low, individually ineffective doses of AP-5 and SCH23390 also prevents learning, suggesting that convergence of both systems on post-synaptic neurons is required In the aforementioned studies, pre-trial blockade of NMDA and D1 receptors appeared to prevent the encoding (or acquisition) of information; however, it is possible that disruption of the consolidation phase of learning or retrieval could have contribut...

show abstract

“…The DNA elements within the human proenkephalin gene that confer responsiveness to second messengers and membrane depolarization have been well characterized (1)(2)(3)(4)(5)(6)(7)(8). To obtain uniform cells for transfection, however, the critical studies of transcriptional mechanism have largely used transformed cell lines (1-7), rather than tissues in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…This element can bind both AP-1 proteins (4, 5, 7) and cAMP response element-binding protein (CREB) (8). In cotransfection models, the proenkephalin gene can be transactivated by AP-1 proteins, including Fos (5) and JunD (7) and by CREB (14), acting via the CRE-2 element (Ref.…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of stress-induced proenkephalin gene regulation: CREB interacts with the proenkephalin gene in the mouse hypothalamus and is phosphorylated in response to hyperosmolar stress

Borsook¹

1994

Molecular Endocrinology

View full text Add to dashboard Cite

We have established a transgenic model to facilitate the study of stress-induced gene regulation in the hypothalamus. This model, which uses a human proenkephalin-β-galactosidase fusion gene, readily permits anatomic and cellular colocalization of stress-regulated immediate early gene products (e.g. Fos) and other transcription factors [e.g. cAMP response element-binding protein (CREB)] with the product of a potential target gene. Moreover, Fos provides a marker of cellular activation that is independent of the transgene. Hypertonic saline stress induced Fos in almost all cells in the PVN that exhibited basal expression of the proenkephalin transgene; however, all cells in which the transgene was activated by stress also expressed Fos. CREB was found in essentially all neurons. Gel shift analysis with and without antisera to Fos and CREB showed that AP-1 binding activity, containing Fos protein, was induced by hyperosmotic stress. However, Fos was not detected binding to the proenkephalin second messenger-inducible enhancer even in hypothalamic cell extracts from stressed animals. In contrast, CREB formed specific complexes with both the proenkephalin enhancer and a cAMP-and calcium-regulated element (CaRE) within the c-fos gene. Moreover, we found that hypertonic saline induced CREB phosphorylation in cells that express the transgene within the paraventricular nucleus and supraoptic nucleus. These results suggest a model in which proenkephalin gene expression in the paraventricular nucleus is regulated by CREB in response to hypertonic stress.

show abstract

The cAMP-response-element-binding protein interacts, but Fos protein does not interact, with the proenkephalin enhancer in rat striatum.

Cited by 132 publications

References 27 publications

Striatal proenkephalin gene induction: coordinated regulation by cyclic AMP and calcium pathways

Striatal proenkephalin gene induction: coordinated regulation by cyclic AMP and calcium pathways

AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: A context-limited role in the encoding and consolidation of instrumental memory

Molecular mechanisms of stress-induced proenkephalin gene regulation: CREB interacts with the proenkephalin gene in the mouse hypothalamus and is phosphorylated in response to hyperosmolar stress

Contact Info

Product

Resources

About