Artificially Enhancing and Suppressing Hippocampus-Mediated Memories

Chen, Briana K.; Murawski, Nathen J.; Cincotta, Christine; McKissick, Olivia; Finkelstein, Abby Basya; Hamidi, Anahita; Merfeld, Emily; Doucette, Emily; Grella, Stephanie L.; Shpokayte, Monika; Zaki, Yosif; Fortin, Amanda; Ramirez, Steve

doi:10.1016/j.cub.2019.04.065

Cited by 85 publications

(92 citation statements)

References 37 publications

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“…In contrast, in c-Fos-tTA transgenic mice (Reijmers et al, 2007) transduced with the DOX-regulated AAV9-TRE-ChR2-eYFP virus, engram labeling was restricted to excitatory neurons, as no overlap was detected somatically between ChR2 positive cells and inhibitory gamma-aminobutyric acid (GABA) positive cells (Liu et al, 2012). To date, no assessment of the kinetics of CNO based neural inactivation has been conducted in wildtype animals that have been injected with the c-Fos-tTA-TRE-hM4Di-eYFP virus, although in a recent paper our group too observed similar results of c-Fos expression in the BLA (Chen et al, 2019).…”

Section: Discussionmentioning

confidence: 70%

Odor Modulates the Temporal Dynamics of Fear Memory Consolidation

Grella

Fortin

McKissick

et al. 2019

Preprint

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Number of words in the abstract: 267 Number of characters w spaces (main text excluding abstract, references & fig legends): 54,606 Grella et al., 2ABSTRACT Systems consolidation (SC) theory proposes that recent, contextually rich memories are stored in the hippocampus (HPC). As these memories become remote, they are believed to rely more heavily on cortical structures within the prefrontal cortex (PFC), where they lose much of their contextual detail and become schematized. Odor is a particularly evocative cue for intense remote memory recall and despite these memories being remote, they are highly contextual. In instances such as post-traumatic stress disorder (PTSD), intense remote memory recall can occur years after trauma, which seemingly contradicts SC. We hypothesized that odor may shift the organization of salient or fearful memories such that when paired with an odor at the time of encoding, they are delayed in the de-contextualization process that occurs across time, and retrieval may still rely on the HPC, where memories are imbued with contextually rich information, even at remote time points. We investigated this by tagging odor-and non-odorassociated fear memories in male c57BL/6 mice and assessed recall and c-Fos expression in the dorsal CA1 (dCA1) and prelimbic cortex (PL) 1 d or 21 d later. In support of SC, our data showed that recent memories were more dCA1-dependent whereas remote memories were more PL-dependent. However, we also found that odor influenced this temporal dynamic biasing the memory system from the PL to the dCA1 when odor cues were present.Behaviorally, inhibiting the dCA1 with activity-dependent DREADDs had no effect on recall at 1 d and unexpectedly caused an increase in freezing at 21 d. Together, these findings demonstrate that odor can shift the organization of fear memories at the systems level.Grella et al., 3

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Section: Discussionmentioning

confidence: 70%

Odor Modulates the Temporal Dynamics of Fear Memory Consolidation

Grella

Fortin

McKissick

et al. 2019

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“…The ACC is important for the expression of remote context fear while the PFC, entorhinal, perirhinal, postrhinal and retrosplenial cortices contribute to recent and remote memory retrieval [12,21,[37][38][39][40]. The ventral hippocampus is also likely to play an important role as it projects to the amygdala and influences the expression of context fear [4,[41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Recently formed context fear memories can be retrieved without the hippocampus

Teratani-Ota

et al. 2019

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The current study determined if inactivation of the dorsal hippocampus impairs the retrieval of newly formed context fear memories. This region was silencing by activating inhibitory neurons or by hyperpolarizing pyramidal cells directly. When inhibitory neurons were stimulated with ChR2, memory retrieval was significantly impaired. In contrast, when the same neurons were activated with the excitatory DREADD hM3Dq, retrieval was not affected. This dissociation was not due to differences in inhibition, as both manipulations activated interneurons and reduced excitation throughout the dorsal hippocampus. Therefore, we hypothesize that the retrieval deficit caused by ChR2 stimulation is due to an immediate reduction in hippocampal activity that does not provide enough time for other brain regions to compensate. Stimulation of DREADDs, on the other hand, produces a gradual loss of excitation that takes several minutes to reach asymptote. This appears to be a sufficient amount of time for extra-hippocampal structures to become engaged and express context fear. Implications for theories of hippocampal function, systems consolidation and memory retrieval are discussed.

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“…Prior studies have captured a memory linked to a specific fear-provoking event/context [45,61,62]. Subsequent manipulation of these engrams has revealed essential aspects of memory and its plasticity [63][64][65][66][67]. While this may have therapeutic potential for disorders linked to a specific traumatic event, such as PTSD, it provides less promise for addressing generalized anxiety disorder (GAD) or fear disorders.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic reactivation of prefrontal social memory trace mimics social buffering of fear

Ahuna

Santos

et al. 2019

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Social buffering occurs when the presence of a companion attenuates the physiological and/or behavioral effects of a stressful or fear-provoking event. It represents a way in which social interactions can immediately and potently modulate behavior. As such, social buffering is one mechanism by which strong social support increases resilience to mental illness. While the behavioral and neuroendocrine impacts of social buffering are well studied in multiple species, including humans, the neuronal bases of this behavioral phenomenon remain largely unexplored. Previous work has shown that the infralimbic prefrontal cortex (IL-PFC) is important for processing social information and, in separate studies, for modulating fear and anxiety. Thus, we hypothesized that socially-active cells within the IL-PFC may integrate social information to modulate fear responsivity. To test this hypothesis, we employed social buffering paradigms in male and female mice. Similar to prior studies in rats, we found that the presence of a cagemate reduced freezing in fear and anxiety-provoking contexts. In accordance with previous work, we demonstrated that interaction with a novel or familiar conspecific induces activity in the IL-PFC as evidenced by increased immediate early gene (IEG) expression. We then utilized an activity-dependent tagging murine line, the ArcCreER T2 mice, to express channelrhodopsin (ChR2) in neurons active during the social encoding of a new cagemate. We found that optogenetic reactivation of these sociallyactive neuronal ensembles phenocopied the effects of cagemate presence in male and female mice in learned and innate fear contexts without being inherently rewarding or altering locomotion. These data suggest that a social neuronal ensemble within the IL-PFC may contribute to social buffering of fear. These neurons may represent a novel therapeutic target for fear and anxiety disorders.

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Artificially Enhancing and Suppressing Hippocampus-Mediated Memories

Cited by 85 publications

References 37 publications

Odor Modulates the Temporal Dynamics of Fear Memory Consolidation

Odor Modulates the Temporal Dynamics of Fear Memory Consolidation

Recently formed context fear memories can be retrieved without the hippocampus

Optogenetic reactivation of prefrontal social memory trace mimics social buffering of fear

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