Identification of Genes Expressed in the Amygdala During the Formation of Fear Memory

Stork, Oliver; Stork, Simone; Pape, Hans‐Christian; Obata, Kunihiko

doi:10.1101/lm.39401

Cited by 75 publications

(62 citation statements)

References 46 publications

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“…PCR-based gene expression analysis confirmed that Ndr2 transcript levels were transiently elevated in the amygdala of fear-conditioned and pseudo-conditioned animals 6 h after training and returned to baseline within 24 h. Thus, during consolidation of fear memory, Ndr2 mRNA levels are regulated in the basolateral complex of the amygdala in a learning-and stress-dependent manner, similar to several other signal transduction and structural re-organization factors (2). GenBank TM analysis suggests that transcription of the Ndr2 gene may be driven through cyclic AMP response elements (CRE) or serum-responsive elements.…”

Section: Discussionmentioning

confidence: 65%

“…1A) was selected from a group of 21 gene products that were differentially expressed in the amygdala during consolidation of fear memory (2). As the first step in our analysis, the induction of Ndr2 expression was confirmed with PCR-based Northern analysis on amygdala samples pooled from each group of four animals (2) (Fig.…”

Section: Isolation and Differential Expression Of Ndr2-mentioning

confidence: 98%

“…A fragment of the Ndr2 3Ј-untranslated region was obtained through subtractive hybridization cloning from the amygdala of fear-conditioned mice (2). PCR-based gene expression analysis confirmed that Ndr2 transcript levels were transiently elevated in the amygdala of fear-conditioned and pseudo-conditioned animals 6 h after training and returned to baseline within 24 h. Thus, during consolidation of fear memory, Ndr2 mRNA levels are regulated in the basolateral complex of the amygdala in a learning-and stress-dependent manner, similar to several other signal transduction and structural re-organization factors (2).…”

Section: Discussionmentioning

confidence: 99%

“…1B). Experiments employed for the identification and expression analysis of clone #VIIE6 have been described previously (2). All animal experiments were performed in accordance with regulations through Japanese and German law and were approved by the Committee for Animal Research, Okazaki National Institutes (permission NRS A11-82-3 and A11-82-65) and the Regierungsprä sidium Dessau (2-375 UNI MD).…”

Section: Methodsmentioning

confidence: 99%

“…We have employed a classic fear conditioning paradigm to isolate candidate genes involved in memory-related functions in the brain (2). Fear conditioning is highly amenable to cellular and molecular approaches to learning and memory, because conditioned subjects (a) very quickly learn to associate a previously neutral sensory stimulus (conditional stimulus) and an aversive, unconditional stimulus during fear conditioning training and (b) develop a robust and easily measurable long term memory after a single training session.…”

mentioning

confidence: 99%

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Neuronal Functions of the Novel Serine/Threonine Kinase Ndr2

Stork

Zhdanov

Kudersky

et al. 2004

Journal of Biological Chemistry

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We have identified a novel member of the Ndr subfamily of serine/threonine protein kinases, Ndr2, as a gene product that is induced in the mouse amygdala during fear memory consolidation and examined a possible function of this kinase in neural differentiation. Expression of Ndr2 mRNA was detected in various cortical and subcortical brain regions, as well as non-neuronal tissues. Its expression in the amygdala was increased 6 h after Pavlovian fear conditioning training and returned to control levels within 24 h. To study intracellular localization and functions of Ndr2, EGFP::Ndr2 fusion proteins were expressed in rat pheochromocytoma (PC12) cells and acutely isolated cortical neurons, thereby revealing an association of Ndr2 with the actin cytoskeleton in somata, neurites and filopodia, in spines and at sites of cell contact. Co-precipitation and pulldown experiments support this finding. Evidence for an involvement of Ndr2 in actin-mediated cellular functions further comes from the observation of decreased cell spreading and changes in neurite outgrowth that were associated with protein serine phosphorylation in transfected PC12 cells. Together, our data suggest that Ndr2 is an interesting candidate gene for the regulation of structural processes in differentiating and mature neuronal cells.Stimulus-dependent modifications of cell structure and connectivity in the central nervous system are basic elements of long term memory formation. Protein kinases and protein phosphatases are key regulators of these processes, which they control and co-ordinate through the phosphorylation and/or dephosphorylation of neurotransmitter receptors and ion channels, cytoskeleton elements, cell surface molecules, and transcription factors (1).We have employed a classic fear conditioning paradigm to isolate candidate genes involved in memory-related functions in the brain (2). Fear conditioning is highly amenable to cellular and molecular approaches to learning and memory, because conditioned subjects (a) very quickly learn to associate a previously neutral sensory stimulus (conditional stimulus) and an aversive, unconditional stimulus during fear conditioning training and (b) develop a robust and easily measurable long term memory after a single training session. Moreover, the neuronal circuits and cellular mechanisms that underlie classic fear conditioning have been investigated in detail (reviewed in Ref.3). These conceptual and technical advantages have allowed researchers to show that, among other factors, protein kinase A, mitogen-activated protein kinase and calcium/calmodulin-dependent kinases are critical for fear conditioning (summarized in Ref. 4). Some of these protein kinase activities could even be tracked down to the amygdala (5-7). Recent evidence further suggests an involvement of Rho-mediated signaling pathways and the Rho-associated kinase (p160 ROCK ) in amygdala plasticity after fear conditioning (8). This pathway may be of particular importance, because it controls actinmediated changes in dendrite and spine...

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Section: Discussionmentioning

confidence: 65%

Section: Isolation and Differential Expression Of Ndr2-mentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Neuronal Functions of the Novel Serine/Threonine Kinase Ndr2

Stork

Zhdanov

Kudersky

et al. 2004

Journal of Biological Chemistry

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Transcriptome changes associated with instructed learning in the barn owl auditory localization pathway

Swofford

DeBello

2007

Developmental Neurobiology

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Owls reared wearing prismatic spectacles learn to make adaptive orienting movements. This instructed learning depends on re-calibration of the midbrain auditory space map, which in turn involves the formation of new synapses. Here we investigated whether these processes are associated with differential gene expression, using longSAGE. Newly fledged owls were reared for 8-36 days with prism or control lenses at which time the extent of learning was quantified by electrophysiological mapping. Transciptome profiles were obtained from the inferior colliculus (IC), the major site of synaptic plasticity, and the optic tectum (OT), which provides an instructive signal that controls the direction and extent of plasticity. Twenty-two differentially expressed sequence tags were identified in IC and 36 in OT, out of more than 35,000 unique tags. Of these, only four were regulated in both structures. These results indicate that regulation of two largely independent gene clusters is associated with synaptic remodeling (in IC) and generation of the instructive signal (in OT). Real-time PCR data confirmed the changes for two transcripts, ubiquitin/polyubiquitin and tyrosine 3-monooxgenase/tryotophan 5-monooxygenase activation protein, theta subunit (YWHAQ; also referred to as 14-3-3 protein). Ubiquitin was downregulated in IC, consistent with a model in which protein degradation pathways act as an inhibitory constraint on synaptogenesis. YWHAQ was up-regulated in OT, indicating a role in the synthesis or delivery of instructive information. In total, our results provide a path towards unraveling molecular cascades that link naturalistic experience with synaptic remodeling and, ultimately, with the expression of learned behavior.

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Effect of MK‐801 on gene expressions in the amygdala of rats

Matsuoka

Tsunoda

Sumiyoshi

et al. 2007

Synapse

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Rodents treated with N-methyl-D-aspartate (NMDA) antagonists have been thought to be an animal model of schizophrenia. In this study, we examined gene expression in the amygdala of rats chronically treated with MK-801, as well as behavioral changes, such as social behavior, in these animals. The social interaction test, a measure of social behavior, and locomotor activity was performed in male Wistar rats injected with MK-801 (0.13 mg/kg i.p.) or saline for 14 days. Changes in mRNA levels were analyzed using a GeneChip microarray system. Real-time quantitative PCR (RT-qPCR) assay was subsequently conducted to confirm the results of the microarray analysis. MK-801 decreased social interaction and increased locomotor activity in rats, consistent with previous reports. We found 23 downregulated genes and 16 upregulated genes, with the gene encoding arginine-vasopressin (AVP) being most downregulated, and that for transthyretin (Ttr) most upregulated. mRNA levels, quantified by RT-qPCR assay, were altered for genes related to neuropeptides (AVP, Sstr2), the arachidonic cascade (Ptgds), myelination (Mobp, Enpp2), neurotrophic factors (Igfbp2), and hormonal milieu (Ttr). Downregulation of the AVP gene in the amygdala of MK-801-treated rats may provide a basis for the ability of AVP-analogues to ameliorate the behavioral disturbances caused by blockade of the NMDA receptor. The results of this study provide an insight into the neural substrates responsible for the generation of psychotic symptoms.

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Identification of Genes Expressed in the Amygdala During the Formation of Fear Memory

Cited by 75 publications

References 46 publications

Neuronal Functions of the Novel Serine/Threonine Kinase Ndr2

Neuronal Functions of the Novel Serine/Threonine Kinase Ndr2

Transcriptome changes associated with instructed learning in the barn owl auditory localization pathway

Effect of MK‐801 on gene expressions in the amygdala of rats

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