Hippocampal cells segregate positive and negative engrams.

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• The hippocampus is crucial for memory, particularly its emotional and spatial aspects.
• Cellular diversity exists along the hippocampus, with the ventral part linked to emotion and valence.
• Recent research highlights the ventral hippocampus's role in processing emotional memory components.

Purpose of the Study:

• To investigate valence-specific memory engrams in the ventral hippocampus (vHPC).
• To identify distinct cellular populations and projection patterns associated with appetitive and aversive experiences.
• To explore the molecular and behavioral underpinnings of these segregated engrams.

Main Methods:

• Utilized transgenic and viral activity-dependent tagging to visualize valence-specific engrams in the vHPC.
• Employed RNA sequencing and DNA methylation sequencing to compare molecular profiles of engram cells.
• Conducted optogenetic manipulations targeting vHPC cell bodies and their projections to downstream areas.

Main Results:

• Identified two partially segregated cell populations and projections in the vHPC responding to appetitive and aversive stimuli.
• Found differential transcriptional programs and DNA methylation landscapes in appetitive and aversive vHPC engram cells compared to neutral ones.
• Demonstrated that stimulating vHPC terminals projecting to the amygdala and nucleus accumbens (NAc) drives behavioral preference or avoidance, unlike projections to the prefrontal cortex (PFC).

Conclusions:

• The vHPC harbors genetically, cellularly, and behaviorally segregated cell populations for appetitive and aversive memory engrams.
• These findings elucidate the neural basis of valence-specific memory processing within the ventral hippocampus.
• The study highlights the importance of specific vHPC projections in mediating emotional valence in memory-related behaviors.