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Invited Symposia

Memory engrams and their implications for human memory

Invited Symposium 2: Sunday, April 14, 2024, 10:00 am – 12:00 pm EDT, Ballroom Center + West

Chair: Denise Cai¹; ¹Mount Sinai
Presenters: Denise Cai, Paul Frankland, Inbal Goshen, Tomás Ryan

Creating stable memories is critical for survival. An animal relies on past learning to navigate its environment, avoid dangerous situations, and find needed resources. Because the environment is dynamic, stable memory engrams must be updated with new information to enable responses to changing threats (a specific danger) and rewards (such as food and water). In this symposium, we will discuss how memories become contextually linked, strengthened, updated, and even forgotten. Dr. Denise Cai will discuss the stability and flexibility of memory engrams using in vivo calcium imaging and chemogenetics to explore how traumatic experiences can alter past (and influence future) memory engrams across a lifetime. Dr. Paul Frankland will highlight the contextual modulation of dentate gyrus ensembles corresponding with context-specific neural states in downstream CA1, and how these internally-generated patterns of activity are sufficient to drive context-appropriate decisions. Dr. Inbal Goshen will discuss the contribution that astrocytes have on strengthening engrams by manipulating the activity of Gq- or Gi- pathways in CA1 astrocytes during memory acquisition, which affect ACC projecting neurons and control behavioral performance. Lastly, Dr. Tomás Ryan will share why forgetting may be an adaptive form of engram plasticity that allows engrams to switch from an accessible to inaccessible state, illustrated through optogenetic stimulation or inhibition to facilitate or prevent the recall of an object memory.

Presentations

Stability and flexibility of memory engrams across a lifetime

Denise Cai¹; ¹Icahn School of Medicine at Mount Sinai

Creating stable memories is critical for survival. An animal relies on past learning to navigate its environment, avoid dangerous situations, and find needed resources. Because the environment is dynamic, stable memories must be updated with new information to enable responses to changing threats (a specific danger) and rewards (such as food and water). The brain circuits involved in memory and learning require both stability and flexibility. Using in vivo calcium imaging and chemogenetics, we discovered that traumatic experiences can alter past memories engrams and have long-lasting changes to how future memory engrams are encoded. This has important implications for how the brain stably stores and flexibly updates memories across the lifetime.

Contextual modulation of memory retrieval

Paul Frankland¹; ¹University of Toronto

Memories of events are linked to the contexts in which they were encoded. This contextual linking ensures enhanced access to those memories that are most relevant to the context at hand, including specific associations that were previously learned in that context. This principle, referred to as encoding specificity, predicts that context-specific neural states should bias retrieval of particular associations over others, potentially allowing for the disambiguation of retrieval cues that may have multiple associations or meanings. Using a context-odor paired associate learning paradigm in mice, here we show that manipulation of dentate gyrus ensembles corresponding to specific contexts reinstates context-specific neural states in downstream CA1, and these internally-generated patterns of activity are sufficient to drive context-appropriate decisions.

Astrocytes control memory strength by affecting the engrams

Inbal Goshen^1,2; ¹Edmond and Lily Safra Center for Brain Sciences (ELSC), ²The Hebrew University of Jerusalem

Recent and remote memories are encoded throughout the brain in 'Engrams': cell ensembles formed during acquisition, and upon their reactivation, a specific memory can be recalled. The maturation of engrams from recent to remote time points involves the recruitment of dorsal CA1 neurons projecting to the anterior cingulate cortex (CA1 to ACC). Various modifications to CA1 astrocytes, to the Gq- or Gi- GPCR pathways, during memory acquisition were shown to affect recent and remote recall in seemingly contradictory ways. We manipulated the activity of either Gq- or Gi- pathways in CA1 astrocytes during memory acquisition and tagged cFos+ engram cells and CA1 to ACC cells during recent and remote recall. The behavioral results were coupled with changes in the recruitment of CA1 to ACC projection cells to the engram. Gq pathway activation in astrocytes caused enhancement of recent recall alone and was accompanied by earlier recruitment of CA1 to ACC projecting cells to the engram. When activating the Gi pathway in astrocytes during acquisition, only remote recall was impaired, and CA1 to ACC projecting cells were not recruited during remote memory. Finally, we provide a simple working model, hypothesizing that astrocytes control behavioral performance by targeting the CA1 to ACC projection. Specifically, that Gq- and Gi- pathway activation affect memory differently, but do so by modulating the same mechanism. These findings illuminate the importance of astrocytes in the acquisition of fear memory and their implications on recent and remote recall.

Forget the Engram - Memory Expression Across Development

Tomás Ryan¹; ¹Trinity College Dublin

Forgetting generally refers to the loss of previously formed memories. Although multiple forms of forgetting have been characterized, ranging from natural "every day" forgetting to unnatural pathological forgetting, a formal scientific framework with which to explain and investigate the neuroscience of forgetting is lacking. This may be because forgetting has been regarded as a defect of the brain, and it has been assumed to have many diverse and incidental causes. However, contemporary research is challenging this paradigm and an alternative perspective has emerged where forgetting may be viewed as an adaptive feature of the brain that allows an organism to respond optimally to its environment. Behavioral studies imply that forgetting serves as an adaptive function to allow organisms to generalize and abstract from initial experiences. Engram cell labeling methodologies allow us to genetically label, observe, and manipulate the specific ensembles of neurons that encode particular memories in the rodent brain. Our recent research on innate and acquired forms of long-term forgetting in the mouse focuses on infantile amnesia during development on one hand, and natural forgetting in adults on the other. Many forms of forgetting are in fact reversible, and that the core information endures within the brain's engrams. I will present a formal model of natural forgetting, based on our empirical data, that will inform future experimental investigations. Finally, I will outline a novel framework that considers both natural and unnatural forgetting to be predictive processes that involve the interaction of a subject's priors with perceptual experience.