c-fos expression in the amygdala:In vivo antisense modulation and role in anxiety

Möller, Christian; Bing, Ola; Heilig, Markus

doi:10.1007/bf02088828

Cited by 35 publications

(12 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in line with an increasing number of studies reporting expression of genes as determinants for altered neuronal activity in the amygdala or other stress-related brain circuits following various stressors (e.g. [23], [24], [33], [34], [35]). A main finding of our study was, however, that even the very short period of only minutes was sufficient for a modified gene regulation leading to measurable changes in the genome-wide expression profiles.…”

Section: Discussionsupporting

confidence: 81%

“…association of the short 5-HTT variant with a relative exaggeration in the response of the amygdala to anxiety-provoking or stress-related stimuli [3], [18], [19], [20], [21], [22]. Further, changes in gene expression accompanying stress reactivity and coping also affect the amygdala, both after acute stress [23], [24], [25], [26] as well as after chronic stress [27], [28]. However, nothing is known about rapid changes in amygdala gene expression following immediately after an acute stressor in case of individuals with an imbalanced serotonergic system that are prone to inappropriate stress response.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Acute Stressor and Serotonin Transporter Genotype on Amygdala First Wave Transcriptome in Mice

Hohoff

Gorji²,

Kaiser

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

The most prominent brain region evaluating the significance of external stimuli immediately after their onset is the amygdala. Stimuli evaluated as being stressful actuate a number of physiological processes as an immediate stress response. Variation in the serotonin transporter gene has been associated with increased anxiety- and depression-like behavior, altered stress reactivity and adaptation, and pathophysiology of stress-related disorders. In this study the instant reactions to an acute stressor were measured in a serotonin transporter knockout mouse model. Mice lacking the serotonin transporter were verified to be more anxious than their wild-type conspecifics. Genome-wide gene expression changes in the amygdala were measured after the mice were subjected to control condition or to an acute stressor of one minute exposure to water. The dissection of amygdalae and stabilization of RNA was conducted within nine minutes after the onset of the stressor. This extremely short protocol allowed for analysis of first wave primary response genes, typically induced within five to ten minutes of stimulation, and was performed using Affymetrix GeneChip Mouse Gene 1.0 ST Arrays. RNA profiling revealed a largely new set of differentially expressed primary response genes between the conditions acute stress and control that differed distinctly between wild-type and knockout mice. Consequently, functional categorization and pathway analysis indicated genes related to neuroplasticity and adaptation in wild-types whereas knockouts were characterized by impaired plasticity and genes more related to chronic stress and pathophysiology. Our study therefore disclosed different coping styles dependent on serotonin transporter genotype even directly after the onset of stress and accentuates the role of the serotonergic system in processing stressors and threat in the amygdala. Moreover, several of the first wave primary response genes that we found might provide promising targets for future therapeutic interventions of stress-related disorders also in humans.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Effect of Acute Stressor and Serotonin Transporter Genotype on Amygdala First Wave Transcriptome in Mice

Hohoff

Gorji²,

Kaiser

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Supporting this hypothesis, Möller et al (1994) reported that c-fos antisense inf used into the amygdala failed to block intracerebroventricular CRH-induced suppression of punished responses, suggesting that the amygdala may not mediate anxiogenic effects induced by intracerebroventricular CRH. Walker and Davis (1996) found that blockade of glutamate receptors in the BNST, but not in the C eA, blocked the unconditioned anxiogenic effects of a bright light (20 min duration), which produces a slowly developing increase in startle amplitude that lasts for a long time once the light is turned off (Walker and Davis, 1997).…”

Section: Implications For a Possible Distinction Between Fear And Anxmentioning

confidence: 94%

Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-Releasing Hormone on the Acoustic Startle Reflex

1997

View full text Add to dashboard Cite

Previously, we demonstrated that transection of the fimbria/ fornix blocked the excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH-enhanced startle), suggesting that the hippocampus and its efferent target areas that communicate via the fimbria may be critically involved in CRHenhanced startle. The bed nucleus of the stria terminalis (BNST) receives direct projections from the ventral hippocampus via the fimbria/fornix. Therefore, the role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced startle was investigated. NMDA lesions of the BNST completely blocked CRH-enhanced startle, whereas chemical lesions of the ventral hippocampus and the amygdala failed to block CRH-enhanced startle. However, the same amygdala-lesioned animals showed a complete blockade of fear-potentiated startle, a conditioned fear response sensitive to manipulations of the amygdala. In contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates a double dissociation between the BNST and the amygdala in two different paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST, but not into the ventral hippocampus, mimicked intracerebroventricular CRH effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH-enhanced startle in a dose-dependent manner. Control studies showed that this blockade did not result from either leakage of the antagonist into the ventricular system or a local anesthetic effect caused by infusion of the antagonist into the BNST. The present studies strongly suggest that CRH in the CSF can activate the BNST, which could lead to activation of brainstem and hypothalamic BNST target areas involved in anxiety and stress responses. Key words: bed nucleus of the stria terminalis (BNST ); amygdala; hippocampus; corticotropin-releasing hormone (CRH); startle; anxiety; fearIntracerebroventricular inf usion of corticotropin-releasing hormone (CRH) elicits a constellation of behavioral, physiological, and endocrinological changes similar to those produced by natural stressors (cf. Dunn and Berridge, 1990). Thus far, however, the exact anatomical sites responsible for these behavioral and physiological actions of CRH after intracerebroventricular administration have not been identified. As part of an effort to delineate the neural circuitry underlying intracerebroventricular CRH effects, recently we investigated a possible involvement of the septum, using increased acoustic startle amplitude after CRH (CRH-enhanced startle) as a behavioral measure (Lee and Davis, 1997). Electrolytic lesions of the whole septum and the medial septum, but not the lateral septum, blocked CRH-enhanced startle. However, fiber-sparing chemical lesions of the medial septum failed to block CRH-enhanced startle, suggesting that the blockade seen with electrolytic lesions was probably caused by damage to fibers of passage, presumably the fornix. Supporting this conclusion, f unctional lesions of the fornix induced by knife cuts of the fimbria /fornix complete...

show abstract

“…In the amygdala, long-term potentiation (LTP), hypothesized to be the mechanism behind some forms of learning, has been demonstrated to require a strong noradrenergic input in order to be established (Huang et al, 2000;Schafe et al, 2001), whereas norepinephrine plays mainly a modulatory role in the hippocampus LTP (Dunwiddie et al, 1982;Sarvey et al, 1989). In both areas, phosphorylation of cyclic AMP response element-binding protein (CREB) and expression of c-Fos are critical in changing gene expression that is important to memory formation (Dragunow et al, 1989;Hall et al, 2001;Moller et al, 1994). The transcription factors P-CREB and c-Fos increase during memory encoding (Tischmeyer and Grimm, 1999), consolidation (Kang et al, 2001), and retrieval (Hall et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…We have addressed this problem and found that the a 2 agonist dexmedetomidine decreases fear memory but not contextual memory. To further understand the mechanism of action by which a 2 ARs may influence fear memory (Hall et al, 2001;Moller et al, 1994), we have assessed dexmedetomidine's affect on c-Fos and P-CREB production in the amygdala. In doing so, we have further elucidated the a 2 adrenoceptor subtype responsible for the observed behavioral action.…”

Section: Introductionmentioning

confidence: 99%

Activation of α2 Adrenergic Receptors Suppresses Fear Conditioning: Expression of c-Fos and Phosphorylated CREB in Mouse Amygdala

Davies

Tsui

Flannery

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

a 2 adrenergic agonists such as dexmedetomidine generally suppress noradrenergic transmission and have sedative, analgesic, and antihypertensive properties. Considering the importance of the neurotransmitter norepinephrine in forming memories for fearful events, we have investigated the acute and chronic effects of dexmedetomidine on discrete cue and contextual fear conditioning in mice. When administered before training, dexmedetomidine (10-20 mg/kg, i.p.) selectively suppressed discrete cue fear conditioning without affecting contextual memory. This behavioral change was associated with a decrease in memory retrieval-induced expression of c-Fos and P-CREB in the lateral, basolateral, and central nuclei of the amygdala. Dexmedetomidine's action on discrete cue memory did not occur in a 2A adrenoceptor knockout (KO) mice. When dexmedetomidine was administered after training, it suppressed contextual memory, an effect that did not occur in a 2A adrenoceptor KO mice. We conclude that dexmedetomidine, acting at a 2A adrenoceptors, must be present during the encoding process to decrease discrete cue fear memory; however, its ability to suppress contextual memory is likely the result of blocking the consolidation process. The ability of a 2 agonists to suppress fear memory may be a valuable property clinically in order to suppress the formation of memories during stressful situations.

show abstract

c-fos expression in the amygdala:In vivo antisense modulation and role in anxiety

Cited by 35 publications

References 22 publications

Effect of Acute Stressor and Serotonin Transporter Genotype on Amygdala First Wave Transcriptome in Mice

Effect of Acute Stressor and Serotonin Transporter Genotype on Amygdala First Wave Transcriptome in Mice

Role of the Hippocampus, the Bed Nucleus of the Stria Terminalis, and the Amygdala in the Excitatory Effect of Corticotropin-Releasing Hormone on the Acoustic Startle Reflex

Activation of α2 Adrenergic Receptors Suppresses Fear Conditioning: Expression of c-Fos and Phosphorylated CREB in Mouse Amygdala

Contact Info

Product

Resources

About