scholarly journals Cholinergic neuronal lesions in the medial septum and vertical limb of the diagonal bands of Broca induce contextual fear memory generalization and impair acquisition of fear extinction

Hippocampus ◽  
2015 ◽  
Vol 26 (6) ◽  
pp. 718-726 ◽  
Author(s):  
Dayan Knox ◽  
Samantha M. Keller
2019 ◽  
Author(s):  
Arnau Sans-Dublanc ◽  
Adrià Razzauti ◽  
Srinidhi Desikan ◽  
Marta Pascual ◽  
Jaime de la Rocha ◽  
...  

AbstractWhether projections from the medial septum regulate the function of the CA1 hippocampus in episodic memory retrieval is not known. Here we show that septal GABAergic inputs to CA1 promote contextual fear memory, blocking the activation of parvalbumin-rich interneurons to facilitate Erk/MAP-kinase signaling in pyramidal cells during retrieval. Thus, suppression of feed-forward inhibition onto CA1 by septal GABAergic neurons gates contextual fear behavior.


2021 ◽  
Author(s):  
Ikumi Mizuno ◽  
Shingo Matsuda ◽  
Suguru Tohyama ◽  
Akihiro Mizutani

The prevalence of post-traumatic stress disorder (PTSD) is higher in women than in men. Among both humans and mice, females exhibit higher resistance to fear extinction than males, suggesting that differences between sexes in processes of fear extinction are involved in the pathophysiology of such fear-related diseases. Sex differences in molecular mechanisms for fear memory and extinction are unclear. The cannabinoid (CB) system is well known to be involved in fear memory and extinction, but this involvement is based mainly on experiments using male rodents. It has been unclear whether there are sex differences in the role of the CB system in fear memory and extinction. To explore the possibility of such differences, we investigated the effects of pharmacological manipulations of the CB system on the retrieval and extinction of contextual fear memory in male and female mice. WIN55,212-2, a CB receptor (CBR) agonist, augmented the retrieval of fear memory in both sexes, but SR141716 (a CB1R antagonist) did not affect it in either sex. An enhancement of 2-arachidonylglycerol (2-AG, one of the two major endocannabinoids) via JZL184 [an inhibitor of the 2-AG hydrolase monoacylglycerol lipase (MAGL)], augmented the retrieval of fear memory through the activation of CB1R but not CB2R in female mice. In contrast, the enhancement of N-arachidonylethanolamine (AEA, the other major endocannabinoid) via URB597, an inhibitor of an AEA hydrolase (fatty acid amide hydrolase-1) did not show any effects on the retrieval or extinction of fear memory in either sex. WIN55,212-2, SR141716, and JZL184 inhibited fear extinction irrespective of sex. These results suggest that although the role of CB1R in the retrieval and extinction of contextual fear memory is common among males and females, the effects of an increase in the 2-AG level on the retrieval of contextual fear memory differ between the sexes.


2018 ◽  
Vol 45 (6) ◽  
pp. 2529-2539 ◽  
Author(s):  
Shuhua Lai ◽  
Gangwei Wu ◽  
Zhixian Jiang

Background/Aims: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Methods: Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. Results: We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Conclusion: Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina F. de Veij Mestdagh ◽  
Jaap A. Timmerman ◽  
Frank Koopmans ◽  
Iryna Paliukhovich ◽  
Suzanne S. M. Miedema ◽  
...  

AbstractHibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.


Author(s):  
Lucas A. Marcondes ◽  
Jociane de C. Myskiw ◽  
Eduarda G. Nachtigall ◽  
Rodrigo F. Narvaes ◽  
Ivan Izquierdo ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xi Yin ◽  
Yuan Gao ◽  
Hai-Shui Shi ◽  
Li Song ◽  
Jie-Chao Wang ◽  
...  

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