scholarly journals Hippocampus and amygdala fear memory engrams re-emerge after contextual fear reinstatement

2019 ◽  
Author(s):  
Yosif Zaki ◽  
William Mau ◽  
Christine Cincotta ◽  
Anahita Hamidi ◽  
Emily Doucette ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Fear Memory ◽  
Neural Substrates ◽  
Memory Representation ◽  
Contextual Fear ◽  
Neuronal Ensembles ◽  
State Present ◽  
Insight Into

AbstractThe formation and extinction of fear memories represent two forms of learning that each engage the hippocampus and amygdala. How cell populations in these areas contribute to fear relapse, however, remains unclear. Here, we demonstrate that, in mice, cells active during fear conditioning in the dentate gyrus of hippocampus and basolateral amygdala exhibit decreased activity during extinction and are re-engaged after fear reinstatement. In vivo calcium imaging reveals that reinstatement drives population dynamics in the basolateral amygdala to revert to a network state similar to the state present during fear conditioning. Finally, we find that optogenetic inactivation of neuronal ensembles active during fear conditioning in either the hippocampus or amygdala is sufficient to disrupt fear expression after reinstatement. These results suggest that fear reinstatement triggers a partial re-emergence of the original fear memory representation, providing new insight into the neural substrates of fear relapse.

scholarly journals Inhibition of the PI3 kinase cascade in corticolimbic circuit: temporal and differential effects on contextual fear and extinction

2013 ◽  
Vol 16 (4) ◽  
pp. 825-833 ◽  
Author(s):  
Milly Kritman ◽  
Mouna Maroun
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Fear Memory ◽  
Fear Learning ◽  
Contextual Fear ◽  
Pi3k Inhibition ◽  
Kinase Cascade ◽  
Differential Involvement ◽  
Phosphoinositide 3 Kinase

Abstract We studied the role of PI3K cascade in the basolateral amygdala (BLA) and the infralimbic region of the medial prefrontal cortex (IL-mPFC), in contextual fear learning and extinction in the rat. To that end, we micro-infused the phosphoinositide-3-kinase (PIK3) inhibitor LY294002 into either the mPFC or the BLA. Infusion of LY294002 into the BLA following fear conditioning was associated with enhanced freezing levels and impaired extinction in the subsequent sessions. Similarly, inhibition of PI3K in the BLA before the retrieval of fear memory was associated with impaired retrieval of the fear memory, which was expressed as reduced freezing levels that persisted over 2 d. In the IL-mPFC, only consolidation of fear extinction was impaired: micro-infusion of PI3K inhibitor following the retrieval of fear was associated with impaired extinction on the following days. These results indicate differences in the temporal parameters of the effects of PI3K inhibition in the IL-mPFC and in the BLA, which suggest differential involvement of these structures in long-term fear and in extinction of fear memory. Our findings provide additional evidence for the critical roles played by PI3K in intact formation of fear memory and in its extinction and add new evidence for a role of PI3K in consolidation of memory of extinction. Better understanding of the differential involvement of the PI3K cascade during acquisition and extinction of fear conditioning in the mPFC-amygdala circuit could potentially contribute to the understanding and treatment of anxiety disorders.

scholarly journals Fear Memory

2016 ◽  
Vol 96 (2) ◽  
pp. 695-750 ◽  
Author(s):  
Ivan Izquierdo ◽  
Cristiane R. G. Furini ◽  
Jociane C. Myskiw
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Inhibitory Avoidance ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Contextual Fear Conditioning ◽  
Fear Learning ◽  
Term Potentiation ◽  
Mechanisms Of Memory

Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre- and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general.

scholarly journals Brain-wide mapping of contextual fear memory engram ensembles supports the dispersed engram complex hypothesis

2019 ◽  
Author(s):  
Dheeraj S Roy ◽  
Young-Gyun Park ◽  
Sachie K Ogawa ◽  
Jae H Cho ◽  
Heejin Choi ◽  
...  
Keyword(s):  
High Probability ◽  
Fear Memory ◽  
Brain Regions ◽  
Memory Recall ◽  
Contextual Fear ◽  
Contextual Fear Memory ◽  
Neuronal Ensembles ◽  
Specific Memory ◽  
Complex Hypothesis ◽  
Memory Engram

Neuronal ensembles that hold specific memory (memory engrams) have been identified in the hippocampus, amygdala, and cortex. It has been hypothesized that engrams for a specific memory are distributed among multiple brain regions that are functionally connected. Here, we report the hitherto most extensive engram map for contextual fear memory by characterizing activity-tagged neurons in 409 regions using SHIELD-based tissue phenotyping. The mapping was aided by a novel engram index, which identified cFos+ brain regions holding engrams with a high probability. Optogenetic manipulations confirmed previously known engrams and revealed new engrams. Many of these engram holding-regions were functionally connected to the CA1 or amygdala engrams. Simultaneous chemogenetic reactivation of multiple engrams, which mimics natural memory recall, conferred a greater level of memory recall than reactivation of a single engram ensemble. Overall, our study supports the hypothesis that a memory is stored in functionally connected engrams distributed across multiple brain regions.

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