Theses Doctoral

Control of Social Aggression through the Hippocampal CA2 Social Novelty Detector

Villegas, Andres

The dorsal CA2 subregion (dCA2) of the hippocampus exerts a critical role in social novelty recognition (SNR) memory and in the promotion of social aggression. Whether the SNR memory and social aggression functions of dCA2 are related or represent independent processes is unknown. Here I investigated the hypothesis that an animal is more likely to attack a novel compared to familiar animal and that dCA2 promotes social aggression through its ability to distinguish between novel and familiar animals.

To test this hypothesis, I conducted a multi-day resident intruder (R-I) test to assess aggression towards familiarized and novel conspecifics. I found that residents were indeed more likely to attack a novel intruder, and that silencing of dCA2 caused a more profound suppression of aggression towards a novel than a familiarized intruder. To explore whether and how dCA2 pyramidal neurons encode aggression, I recorded calcium signals from resident dCA2 pyramidal neurons using microendoscopy during the R-I test. I found that a fraction of dCA2 neurons were selectively activated or inhibited during exploration, dominance, and attack behaviors and that the responses varied with conspecific novelty. Based on dCA2 population activity, a set of binary linear classifiers could accurately predict whether an animal was engaged in each of these forms of social behavior. Notably, the accuracy of decoding aggression was greater for novel compared to familiar intruders.

Moreover, calcium signals were more highly correlated during R-I tests with the same familiarized intruder on successive days compared to R-I tests with a familiar and novel intruder on successive days. Similarly, I found significant cross-day decoding results during attack-related behaviors towards familiar-familiar but not for familiar-novel intruder pairs. Together, these findings demonstrate that dCA2 integrates social experience to guide future behavior and provides insight into how SNR memory adaptively influences aggressive behavior. Encounters with novel intruders generally promote aggression while familiarization leads to its stabilization. Moreover, my results are consistent with the hypothesis that dCA2 promotes aggression by computing social novelty.

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More About This Work

Academic Units
Neurobiology and Behavior
Thesis Advisors
Siegelbaum, Steven A.
Degree
Ph.D., Columbia University
Published Here
April 24, 2024