Hippocampal Engrams Generate Variable Behavioral Responses and Brain-Wide Network States.

Freezing is a defensive behavior commonly examined during hippocampal-mediated fear engram reactivation. How these cellular populations engage the brain and modulate freezing across varying environmental demands is unclear. To address this, we optogenetically reactivated a fear engram in the dentate gyrus subregion of the hippocampus across three distinct contexts in male mice.

Chronic Gq activation of ventral hippocampal neurons and astrocytes differentially affects memory and behavior.

Network dysfunction is implicated in numerous diseases and psychiatric disorders, and the hippocampus serves as a common origin for these abnormalities. To test the hypothesis that chronic modulation of neurons and astrocytes induces impairments in cognition, we activated the hM3D(Gq) pathway in CaMKII+ neurons or GFAP+ astrocytes within the ventral hippocampus across 3, 6, and 9 months. CaMKII-hM3Dq activation impaired fear extinction at 3 months and acquisition at 9 months.

Social reactivation of fear engrams enhances memory recall.

For group-living animals, the social environment provides salient experience that can weaken or strengthen aspects of cognition such as memory recall. Although the cellular substrates of individually acquired fear memories in the dentate gyrus (DG) and basolateral amygdala (BLA) have been well-studied and recent work has revealed circuit mechanisms underlying the encoding of social experience, the processes by which social experience interacts with an individual’s memories to alter recall remain unknown. Here we show that stressful social experiences enhance the recall of previously acquired fear memories in male but not female mice, and that social buffering of conspecifics’ distress blocks this enhancement.

Linking Social Cognition to Learning and Memory.

Many mammals have evolved to be social creatures. In humans, the ability to learn from others' experiences is essential to survival; and from an early age, individuals are surrounded by a social environment that helps them develop a variety of skills, such as walking, talking, and avoiding danger. Similarly, in rodents, behaviors, such as food preference, exploration of novel contexts, and social approach, can be learned through social interaction.

Social behavior in mice following chronic optogenetic stimulation of hippocampal engrams.

The hippocampus processes both spatial-temporal information and emotionally salient experiences. To test the functional properties of discrete sets of cells in the dorsal dentate gyrus (dDG), we examined whether chronic optogenetic reactivation of these ensembles was sufficient to modulate social behaviors in mice. We found that chronic reactivation of discrete dDG cell populations in male mice largely did not affect social behaviors in an experience-dependent manner.

Odor modulates the temporal dynamics of fear memory consolidation.

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.