Behavioral analysis of CREB αΔ mutation on a B6/129 F1 hybrid background

Graves, Laurel A.; Dalvi, Ashutosh; Lucki, Irwin; Blendy, Julie A.; Abel, Ted

doi:10.1002/hipo.10003

Cited by 97 publications

(91 citation statements)

References 49 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results underscore the complexity of the genetics and transcription factor balance underlying such behaviors, as CREB-deficient mice have increased the levels of both activator and repressor CREM isoforms and given that lack of CREM leads to an apparently contrasting phenotype (Maldonado et al, 1999). In agreement with our results, mice with Creb1 aD mutation on a defined B6/129F1 background have also been reported to show anxiogeniclike responses in the elevated plus maze (Graves et al, 2002). Furthermore, a decrease in CREB function in the central amygdala has been described to be a common factor in anxiety and alcohol abuse disorders .…”

Section: ) Insupporting

confidence: 90%

“…Other work utilizing antisense oligonucleotides has also implicated decreased CREB expression in the LC with attenuated withdrawal and electrophysiological responses (Lane-Ladd et al, 1997). On the other hand, local changes in CREB activity in the nucleus accumbens alters reactions to anxiogenic, aversive, and nociceptive stimuli Graves et al, 2002;Pandey et al, 2003;Pandey, 2003), whereas it has also been reported that the aversive properties of morphine are present in CREB mutant mice (Walters and Blendy, 2001).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of Anxiety-Like Behavior and Morphine Dependence in CREB-Deficient Mice

Valverde

Mantamadiotis

Torrecilla

et al. 2004

Neuropsychopharmacol

113

View full text Add to dashboard Cite

The transcription factor cAMP-responsive element binding protein (CREB) has been shown to regulate different physiological responses including drug addiction and emotional behavior. Molecular changes including adaptive modifications of the transcription factor CREB are produced during drug dependence in many regions of the brain, including the locus coeruleus (LC), but the molecular mechanisms involving CREB within these regions have remained controversial. To further investigate the involvement of CREB in emotional behavior, drug reward and opioid physical dependence, we used two independently generated CREB-deficient mice. We employed the Cre/loxP system to generate mice with a conditional CREB mutation restricted to the nervous system, where all CREB isoforms are lacking in the brain (Creb1 NesCre ). A genetically defined cohort of the previously described hypomorphic Creb1 aD mice, in which the two major transcriptionally active isoforms (a and D) are disrupted throughout the organism, were also used. First, we investigated the responses to stress of the CREB-deficient mice in several paradigms, and we found an increased anxiogenic-like response in the both Creb1 mutant mice in different behavioral models. We investigated the rewarding properties of drugs of abuse (cocaine and morphine) and natural reward (food) using the conditioned place-preference paradigm. No modification of motivational responses of morphine, cocaine, or food was observed in mutant mice. Finally, we evaluated opioid dependence by measuring the behavioral expression of morphine withdrawal and electrophysiological recordings of LC neurons. We showed an important attenuation of the behavioral expression of abstinence and a decrease in the hyperactivity of LC neurons in both Creb1 mutant mice. Our results emphasize the selective role played by neuronal CREB in emotional-like behavior and the somatic expression morphine withdrawal, without participating in the rewarding properties induced by morphine and cocaine.

show abstract

Section: ) Insupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Modulation of Anxiety-Like Behavior and Morphine Dependence in CREB-Deficient Mice

Valverde

Mantamadiotis

Torrecilla

et al. 2004

Neuropsychopharmacol

113

View full text Add to dashboard Cite

show abstract

“…Male C57BL/6J mice bred in our animal facility from mice originally obtained from The Jackson Laboratory (Bar Harbor, ME) were used in most experiments. For studies using CREB␣⌬ mutant mice, experimental mice were male and female wild-type and homozygous products of F1 crosses of CREB␣⌬ ϩ/Ϫ C57BL/6J with CREB␣⌬ ϩ/Ϫ 129/ SvEvTac mice (as by Graves et al, 2002). The CREB␣⌬ mutation (Hummler et al, 1994) had been backcrossed in a heterozygous state in each parental strain for 9 -11 generations.…”

Section: Methodsmentioning

confidence: 99%

“…The CREB␣⌬ mutation (Hummler et al, 1994) had been backcrossed in a heterozygous state in each parental strain for 9 -11 generations. Genotyping was performed as described previously (Graves et al, 2002). Cbp KIX/KIX knock-in mice were generated as described previously (Kasper et al, 2002;Wood et al, 2006) and were generously provided by Dr. Paul Brindle (St. Jude Children's Research Hospital, Memphis, TN).…”

Section: Methodsmentioning

confidence: 99%

“…Given this potential modulation of CREB-mediated transcription by histone acetylation, we hypothesized that CREB might have a role in the enhancement of memory and E-LTP after HDAC inhibition. We examined mice with targeted deletions of the ␣ and ⌬ isoforms of Creb (CREB␣⌬ mice) on a defined F1 hybrid genetic background (C57BL/6J and 129/SvEvTac) (Walters and Blendy, 2001;Graves et al, 2002). CREB␣⌬ mutant mice and wild-type CREB ϩ/ϩ littermates were fitted with intrahippocampal cannulas and subjected to contextual fear conditioning.…”

Section: Creb Is Required For the Enhancement Of Memory And Synaptic mentioning

confidence: 99%

See 1 more Smart Citation

Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation

Vecsey¹,

Hawk²,

Lattal³

et al. 2007

Journal of Neuroscience

Self Cite

759

761

View full text Add to dashboard Cite

Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance both memory and synaptic plasticity. The current model for the action of HDAC inhibitors assumes that they alter gene expression globally and thus affect memory processes in a nonspecific manner. Here, we show that the enhancement of hippocampus-dependent memory and hippocampal synaptic plasticity by HDAC inhibitors is mediated by the transcription factor cAMP response element-binding protein (CREB) and the recruitment of the transcriptional coactivator and histone acetyltransferase CREB-binding protein (CBP) via the CREB-binding domain of CBP. Furthermore, we show that the HDAC inhibitor trichostatin A does not globally alter gene expression but instead increases the expression of specific genes during memory consolidation. Our results suggest that HDAC inhibitors enhance memory processes by the activation of key genes regulated by the CREB:CBP transcriptional complex.

show abstract

The Role of CREB and CBP in Brain Function

Barco

Kandel

2005

Transcription Factors in the Nervous System

View full text Add to dashboard Cite

In this chapter, the various functions in the nervous system of the CRE-binding protein (CREB), its paralogues CREM and ATF1, and its co-activator the CREB-binding protein (CBP), are reviewed. A wide array of techniques, including mouse transgenesis, gene targeting, genome-wide analyses and behavioral and electrophysiological studies, have revealed an important role for the CREB activation pathway in different brain functions. These studies have clarified our understanding of the mechanisms whereby CREB activity is regulated and have provided essential clues about how the same family of transcription factors can mediate such apparently distinct biological functions as memory storage, neuroprotection, and drug addiction. 11.1208 11 The Role of CREB and CBP in Brain Function demonstrated that CBP also interacts with other transcription factors, and thereby participates in other essential biological processes, including the control of a variety of neuronal responses.In this chapter, we describe selected aspects of our understanding of the functions of the CREB activation pathway in the nervous system, focusing in particular on the roles of CREB and CBP proteins. A number of excellent articles have reviewed this area [3][4][5][6][7][8][9]. Here, we will focus on the central nervous system, where CREB has been implicated, in the mechanisms of activity-dependent synaptic plasticity [10,11], neurogenesis [12], neuronal survival [13, 14], synaptic refinement during development [15], drug addiction [16, 17], circadian rhythm [18], and depression [19]. The CREB Family of Transcription Factors CREB Family Members and Close FriendsThe genes Creb, Crem, and Atf-1 encode for a group of highly homologous proteins that is frequently referred as the CREB family of transcription factors. This family is characterized by a conserved basic region/leucine zipper (bZIP) domain that bind to CRE sites found in one or several copies in the promoters of many genes (Figs. 11.1 and 11.2). CREB and ATF1 are the two most abundant CRE-binding proteins expressed in neurons, and are expressed ubiquitously throughout the nervous system and elsewhere. In contrast, CREM is expressed primarily in the neuroendocrine system [3]. However, these three proteins are not the only transcription factors known to bind to CRE sites. Other factors also bind to these sites and contribute to regulate cAMP-mediated gene expression. These other factors share many structural features with the CREB family, and the larger group is frequently referred to as the ATF/CREB family of transcription factors. This larger family includes not only the CREB family, as a subgroup, but also other bZIP proteins such as ATF2, ATF3, and ATF4. Different ATF/CREB proteins can form selective heterodimers with each other, and also with other transcription factors such as AP-1 and C/EBP that do not belong to this family but share a bZIP DNA-binding domain. Members of different families may compete for the same DNA sites and form heterodimers with members of other families. As has occurr...

show abstract

Behavioral analysis of CREB αΔ mutation on a B6/129 F1 hybrid background

Cited by 97 publications

References 49 publications

Modulation of Anxiety-Like Behavior and Morphine Dependence in CREB-Deficient Mice

Modulation of Anxiety-Like Behavior and Morphine Dependence in CREB-Deficient Mice

Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation

The Role of CREB and CBP in Brain Function

Contact Info

Product

Resources

About