scholarly journals Reactivating Hippocampal-Mediated Memories to Disrupt the Reconsolidation of Fear

2021 ◽  
Author(s):  
Stephanie L Grella ◽  
Amanda H Fortin ◽  
John H Bladon ◽  
Leanna F Reynolds ◽  
Evan Ruesch ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Conditioned Fear ◽  
Large Population ◽  
Fear Memory ◽  
Memory Recall ◽  
Negative Experiences ◽  
Operant Responding ◽  
Small Set ◽  
The Brain ◽  
Stimulation Of

Memories are stored in the brain as cellular ensembles activated during learning and reactivated during retrieval. Using the Tet-tag system, we labeled dorsal dentate gyrus (dDG) neurons activated by positive, neutral or negative experiences with channelrhodopsin-2. Following fear-conditioning, these cells were artificially reactivated during fear memory recall. Optical stimulation of a competing positive memory was sufficient to disrupt reconsolidation, thereby reducing conditioned fear acutely and enduringly. Moreover, mice demonstrated operant responding for reactivation of a positive memory, confirming its reward-like properties. These results show that interference from a rewarding experience can counteract negative states. While interference induced by memory reactivation involved a relatively small set of neurons, we also found that activating a large population of randomly labeled dDG neurons was effective at disrupting fear reconsolidation. Importantly, reconsolidation-interference was specific to the fear memory. These findings implicate the dDG as a potential therapeutic node for modulating memories to suppress fear.

scholarly journals Reactivating Hippocampal-Mediated Memories to Disrupt the Reconsolidation of Fear

2021 ◽  
Author(s):  
Stephanie Grella ◽  
Amanda Fortin ◽  
John Bladon ◽  
Leanna Reynolds ◽  
Evan Ruesch ◽  
...  
Keyword(s):  
Conditioned Fear ◽  
Large Population ◽  
Fear Memory ◽  
Affective States ◽  
Negative Experiences ◽  
Operant Responding ◽  
Small Set ◽  
Negative Affective States ◽  
The Brain ◽  
Stimulation Of

Abstract Memories are stored in the brain as cellular ensembles activated during learning and reactivated during retrieval. Using the Tet-tag system, we labeled dorsal dentate gyrus (dDG) neurons activated by positive, neutral or negative experiences with channelrhodopsin-2. Following fear-conditioning, these cells were artificially reactivated during fear memory recall. Optical stimulation of a competing positive memory was sufficient to disrupt reconsolidation, thereby reducing conditioned fear acutely and enduringly. Moreover, mice demonstrated operant responding for reactivation of a positive memory, confirming its rewarding properties. These results show that interference from a rewarding experience can counteract negative affective states. While interference induced by memory reactivation involved a relatively small set of neurons, we also found that activating a large population of randomly labeled dDG neurons was effective at disrupting reconsolidation. Importantly, reconsolidation-interference was specific to the fear memory. These findings implicate the dDG as a potential therapeutic node for modulating memories to suppress fear.

Synapse-specific representation of the identity of overlapping memory engrams

Science ◽  
2018 ◽  
Vol 360 (6394) ◽  
pp. 1227-1231 ◽  
Author(s):  
Kareem Abdou ◽  
Mohammad Shehata ◽  
Kiriko Choko ◽  
Hirofumi Nishizono ◽  
Mina Matsuo ◽  
...  
Keyword(s):  
Retrograde Amnesia ◽  
Fear Memory ◽  
Memory Recall ◽  
Optogenetic Stimulation ◽  
Specific Memory ◽  
Memory Engram ◽  
And Storage ◽  
The Brain ◽  
Cell Ensemble ◽  
Stimulation Of

Memories are integrated into interconnected networks; nevertheless, each memory has its own identity. How the brain defines specific memory identity out of intermingled memories stored in a shared cell ensemble has remained elusive. We found that after complete retrograde amnesia of auditory fear conditioning in mice, optogenetic stimulation of the auditory inputs to the lateral amygdala failed to induce memory recall, implying that the memory engram no longer existed in that circuit. Complete amnesia of a given fear memory did not affect another linked fear memory encoded in the shared ensemble. Optogenetic potentiation or depotentiation of the plasticity at synapses specific to one memory affected the recall of only that memory. Thus, the sharing of engram cells underlies the linkage between memories, whereas synapse-specific plasticity guarantees the identity and storage of individual memories.

Reactivation of recall-induced neurons contributes to remote fear memory attenuation

Science ◽  
2018 ◽  
Vol 360 (6394) ◽  
pp. 1239-1242 ◽  
Author(s):  
Ossama Khalaf ◽  
Siegfried Resch ◽  
Lucie Dixsaut ◽  
Victoire Gorden ◽  
Liliane Glauser ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Memory Trace ◽  
Fear Memory ◽  
Memory Recall ◽  
Fear Reduction ◽  
Specific Manner ◽  
Induced Neurons ◽  
Standing Question ◽  
Memory Attenuation

Whether fear attenuation is mediated by inhibition of the original memory trace of fear with a new memory trace of safety or by updating of the original fear trace toward safety has been a long-standing question in neuroscience and psychology alike. In particular, which of the two scenarios underlies the attenuation of remote (month-old) fear memories is completely unknown, despite the impetus to better understand this process against the backdrop of enduring traumata. We found—chemogenetically and in an engram-specific manner—that effective remote fear attenuation is accompanied by the reactivation of memory recall–induced neurons in the dentate gyrus and that the continued activity of these neurons is critical for fear reduction. This suggests that the original memory trace of fear actively contributes to remote fear attenuation.

scholarly journals Metabolic fingerprints of fear memory consolidation during sleep

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Iyo Koyanagi ◽  
Kazuhiro Sonomura ◽  
Toshie Naoi ◽  
Takaaki Ohnishi ◽  
Naoko Kaneko ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Memory Consolidation ◽  
Conditioned Fear ◽  
Fear Memory ◽  
State Transitions ◽  
Contextual Fear ◽  
Memory Processing ◽  
Contextual Fear Memory ◽  
Purine Metabolites ◽  
Wake State

AbstractMetabolites underlying brain function and pathology are not as well understood as genes. Here, we applied a novel metabolomics approach to further understand the mechanisms of memory processing in sleep. As hippocampal dentate gyrus neurons are known to consolidate contextual fear memory, we analyzed real-time changes in metabolites in the dentate gyrus in different sleep–wake states in mice. Throughout the study, we consistently detected more than > 200 metabolites. Metabolite profiles changed dramactically upon sleep–wake state transitions, leading to a clear separation of phenotypes between wakefulness and sleep. By contrast, contextual fear memory consolidation induced less obvious metabolite phenotypes. However, changes in purine metabolites were observed upon both sleep–wake state transitions and contextual fear memory consolidation. Dietary supplementation of certain purine metabolites impaired correlations between conditioned fear responses before and after memory consolidation. These results point toward the importance of purine metabolism in fear memory processing during sleep.

scholarly journals Immunohistochemical Characteristics of Ischemic Process in Hippocampal Formation in Posterity of Female Rats after Labor Induction

2021 ◽  
Vol 6 (3) ◽  
pp. 114-119
Author(s):  
I. Yu. Mamay ◽  
◽  
O. A. Hryhorieva ◽  
V. I. Dariy
Keyword(s):  
Monoclonal Antibody ◽  
Glial Fibrillary Acidic Protein ◽  
Dentate Gyrus ◽  
Hippocampal Formation ◽  
Acidic Protein ◽  
Female Rats ◽  
Relative Area ◽  
Santa Cruz ◽  
The Brain ◽  
Stimulation Of

The response to perinatal hypoxia, developing in stimulating generic activity, is the activation of microglia, which induces the development of local inflammation of the brain and leads to the death of neurons. The formation of the hippocampus supports important physiological and behavioral functions, including spatial learning and memory, and is part of the brain, which is especially vulnerable to changes in blood glucose and oxygen. Thus, the study of the features of the development of hippocampal formation in the postnatal period after stimulating generic activity is relevant. The purpose of the study was to study the features of Glial fibrillary acidic protein and NeuN expression in the hippocampal formation in posterity of female rats after PgE2 injection for labor induction. Materials and methods. Pregnant females of the experimental group on the twenty-second day of pregnancy were injected intravaginally with PGE2 in the form of a gel to stimulate the generic activity. Birth occurred on the twenty-third day after conception. Birth in the intact group of rats occurred on the 23-24th day after conception. The large hemispheres of the rat brain were fixed in a 10% neutral formal solution, dehydrated in an ascending alcohol battery. For immunohistochemical studies, paraffin sections were used with 3 microns with a thickness of 3 microns. Glial fibrillary acidic protein Mouse Monoclonal Antibody (Santa Cruz Biotechnology, Inc.) is used to detect astrocytes (Santa Cruz Biotechnology, Inc.). NeuN Mouse Monoclonal Antibody (Santa Cruz Biotechnology, Inc.) was used to identify neurons on the 1st, 7th, 14th, 45th days after birth in histological cuts of hippocampus and gear, using a program for analyzing and processing images Image J, studied the relative area occupied by Glial fibrillary acidic protein + NeuN + cells. Data is processed by variation statistics. The results are reliable at p <0.05. All animal experiments were performed according to international principles of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes” (Strasbourg, 18.03.86) and the Law of Ukraine No. 1759-VI (15.12.2009) On the Protection of Animals from Cruelty. Results and discussion. We identified that by the changes in the hippocampus and the toothed gyrus of the rats after induction of labor, increased Glial fibrillary acidic protein expression on the first day after birth and reducing the NeuN expression on the 14th and 45th day of life in experimental animals compared to the control group were included. Conclusion. The density of the distribution of Glial fibrillary acidic protein + cells in the hippocampus and the dentate gyrus of rats changes wavily throughout the first month and a half of postnatal life. In the offspring of rats, after stimulation of labor on the first day of life, a reliable increase in the relative area occupied by Glial fibrillary acidic protein + astrocytes is determined compared to the control (49.3±2.6% and 36.8±5.9%, respectively). In the hippocampus and the dentate gyrus of rats after stimulation of labor during the first 45 days after birth, the gradual decrease in the relative area occupied by NeuN + neurons is determined, in contrast to the control animals, in which this index practically does not change. On the 14th and 45th days, the index of the relative area occupied by NeuN + neurons in experimental rats is reliably lower than in control (p <0.05).

scholarly journals Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala

2016 ◽  
Vol 84 (10) ◽  
pp. 2861-2870 ◽  
Author(s):  
Fumiaki Ihara ◽  
Maki Nishimura ◽  
Yoshikage Muroi ◽  
Motamed Elsayed Mahmoud ◽  
Naoaki Yokoyama ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Chronic Infection ◽  
Conditioned Fear ◽  
Parasite Load ◽  
Fear Memory ◽  
Epidemiological Studies ◽  
Content Type ◽  
Dopamine Metabolites ◽  
Toxoplasma Gondii Infection ◽  
The Brain

Chronic infection withToxoplasma gondiibecomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found thatT. gondiiinfection impairs consolidation of conditioned fear memory. To examine the brain pathology induced byT. gondiiinfection, we analyzed the parasite load and histopathological changes.T. gondiiinfects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest thatT. gondiiinfection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen duringT. gondiiinfection.

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