scholarly journals The Conditions under Which Consolidation of Serial-Order Conditioned Fear Requires De Novo Protein Synthesis in the Basolateral Amygdala Complex

2019 ◽  
Vol 39 (37) ◽  
pp. 7357-7368 ◽  
Author(s):  
Matthew J. Williams-Spooner ◽  
R. Frederick Westbrook ◽  
Nathan M. Holmes
2020 ◽  
Author(s):  
Prerana Shrestha ◽  
Zhe Shan ◽  
Maggie Marmarcz ◽  
Karen San Agustin Ruiz ◽  
Adam Taye Zerihoun ◽  
...  

To survive in a dynamic environment, animals need to identify and appropriately respond to stimuli that signal danger1,2. At the same time, animal survival also depends on suppressing the threat response during a stimulus that predicts absence of threat, i.e. safety3-5. Understanding the biological substrates of differential threat memories in which animals learn to flexibly switch between expressing and suppressing defensive responses to a threat-predictive cue and a safety cue, respectively, is critical for developing treatments for memory disorders such as PTSD6. A key brain area for processing and storing threat memories is the centrolateral amygdala (CeL), which receives convergent sensory inputs from the parabrachial nucleus and the basolateral amygdala and connects directly to the output nucleus of amygdala, the centromedial nucleus, to mediate defensive responses7-9. Despite a plethora of studies on the importance of neuronal activity in specific CeL neuronal populations during memory acquisition and retrieval10-12, little is known about regulation of their protein synthesis machinery. Consolidation of long-term, but not short-term, threat memories requires de novo protein synthesis, which suggests that the translation machinery in CeL interneurons is tightly regulated in order to stabilize associative memories. Herein, we have applied intersectional chemogenetic strategies in CeL interneurons to block cell type-specific translation initiation programs that are sensitive to depletion of eukaryotic initiation factor 4E (eIF4E) and phosphorylation of eukaryotic initiation factor 2α (p-eIF2α), respectively. We show that in a differential threat conditioning paradigm, de novo translation in somatostatin-expressing (SOM) interneurons in the CeL is necessary for long-term storage of conditioned threat response whereas de novo translation in protein kinase Cδ-expressing (PKCδ) interneurons in the CeL is essential for storing conditioned response inhibition to a safety cue. Further, we show that oxytocinergic neuromodulation of PKCδ interneurons during differential threat learning is important for long-lasting cued threat discrimination. Our results indicate that the molecular elements of a differential threat memory trace are compartmentalized in distinct CeL interneuron populations and provide new mechanistic insight into the role of de novo protein synthesis in consolidation of long-term memories.


2002 ◽  
Vol 76 (15) ◽  
pp. 7578-7586 ◽  
Author(s):  
Bodil Øster ◽  
Per Höllsberg

ABSTRACT Herpesvirus gene expression is divided into immediate-early (IE) or α genes, early (E) or β genes, and late (L) or γ genes on the basis of temporal expression and dependency on other gene products. By using real-time PCR, we have investigated the expression of 35 human herpesvirus 6B (HHV-6B) genes in T cells infected by strain PL-1. Kinetic analysis and dependency on de novo protein synthesis and viral DNA polymerase activity suggest that the HHV-6B genes segregate into six separate kinetic groups. The genes expressed early (groups I and II) and late (groups V and VI) corresponded well with IE and L genes, whereas the intermediate groups III and IV contained E and L genes. Although HHV-6B has characteristics similar to those of other roseoloviruses in its overall gene regulation, we detected three B-variant-specific IE genes. Moreover, genes that were independent of de novo protein synthesis clustered in an area of the viral genome that has the lowest identity to the HHV-6A variant. The organization of IE genes in an area of the genome that differs from that of HHV-6A underscores the distinct differences between HHV-6B and HHV-6A and may provide a basis for further molecular and immunological analyses to elucidate their different biological behaviors.


2004 ◽  
Vol 31 (8) ◽  
pp. 847 ◽  
Author(s):  
Tae-Hwan Kim ◽  
Bok-Rye Lee ◽  
Woo-Jin Jung ◽  
Kil-Yong Kim ◽  
Jean-Christophe Avice ◽  
...  

The kinetics of protein incorporation from newly-absorbed nitrogen (N, de novo protein synthesis) was estimated by 15N tracing in 18-week-old white clover plants (Trifolium repens L. cv. Regal) during 7 d of water-deficit treatment. The physiological relationship between kinetics and accumulation of proline and ammonia in response to the change in leaf-water parameters was also assessed. All leaf-water parameters measured decreased gradually under water deficit. Leaf and root dry mass was not significantly affected during the first 3 d when decreases in leaf-water parameters were substantial. However, metabolic parameters such as total N, proline and ammonia were significantly affected within 1 d of commencement of water-deficit treatment. Water-deficit treatment significantly increased the proline and NH3–NH4+ concentrations in both leaves and roots. There was a marked reduction in the amount of N incorporated into the protein fraction from the newly absorbed N (NANP) in water-deficit stressed plants, particularly in leaf tissue. This reduction in NANP was strongly associated with an increased concentration of NH3–NH4+ in roots (P≤0.05) and proline (P≤0.01) in leaves and roots. These results suggest that proline accumulation may be a sensitive biochemical indicator of plant water status and of the dynamics of de novo protein synthesis in response to stress severity.


Author(s):  
Margarita Elena Papandreou ◽  
Konstantinos Palikaras ◽  
Nektarios Tavernarakis

2002 ◽  
Vol 87 (04) ◽  
pp. 674-683 ◽  
Author(s):  
John Martens ◽  
Lambert Dorssers ◽  
Jan Klijn ◽  
John Foekens ◽  
Anieta Sieuwerts

SummaryIn breast stroma urokinase plasminogen activator (uPA) is predominantly expressed by fibroblasts located in the near vicinity of tumor cells, and fibroblast-derived insulin-like growth factor-1 (IGF-1) may be involved in inhibiting the expression of uPA in these fibroblasts. To investigate a possible role for fibroblast growth factors (FGFs), we evaluated the expression of components of the PA system and the IGF system in normal and tumor-tissue-derived human breast fibroblasts exposed to various FGFs in vitro. mRNA analysis revealed that FGF-1, FGF-2 and FGF-4 induced the mRNA expression levels of uPA, tPA, uPAR, PAI-1 and PAI-2, and reduced those of IGF-1, IGF-1R, IGF-2R and IGFBP-4, without significantly affecting the levels of IGFBP-3, IGFBP-5 and IGFBP-6 mRNA. Concerning the expression of IGF-2 mRNA, the effects mediated by FGF-1, FGF-2 and FGF-4 were divergent. In general, the effects elicited by FGF-1 on the various mRNA levels studied were rapid and short-term. Those mediated by FGF-2 overall lagged behind but were longer-lasting. For FGF-4 an in between pattern was observed. Blocking transcription and translation demonstrated that a) both the FGF-1 and FGF-2 induced effects were the result of altered gene transcription or mRNA stability, b) the short-term effects mediated by FGF-1 and FGF-2 required de novo protein synthesis, and c) the long-term effects elicited by FGF-2 did not depend on de novo protein synthesis during the first 24 h, but were triggered by proteins produced or made available thereafter. The data presented propose that of the FGFs studied (FGF-1, -2, -4, -5, and -7), FGF-2 is the most attractive target for therapeutical strategies aimed at diminishing the contribution of stromal fibroblasts in the PA-directed breast tumor proteolysis.


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