Newswise — Scientists from the Center for Cognition and Sociality (CCS) at the Institute for Basic Science (IBS) recently revealed the identification of neurons enabling recognition of others. The team found that the neurons responsible for processing information related to distinct individuals reside in the CA1 area of the hippocampus.

Social beings, like humans, consistently partake in social exchanges. Within this realm, the capacity to acknowledge the identity of the social partner, retrieve pertinent details from memory, and incorporate new information from ongoing interactions holds paramount importance in forming social connections. Nevertheless, investigations into the neural mechanisms underlying these processes have been relatively scarce.

Historical endeavors to address this inquiry primarily concentrated on examining the brains of mice, with a specific emphasis on the hippocampus. The hippocampus was perceived as a plausible candidate due to its established role in memory consolidation. Among the subdivisions of the hippocampus, namely CA1 to CA3, the Cornu Ammonis (CA) fields garnered significant attention as they are known to play crucial roles in memory-related functions and spatial processing.

Until now, investigations into the neural processes underlying individual recognition in mice have primarily centered on the CA2 region of the hippocampus. Nevertheless, previous studies have primarily relied on behavioral experiments that solely involve discerning unfamiliar mice from familiar ones. This limitation makes it challenging to definitively ascertain whether the observed outcomes genuinely reflect the animals' capability to perceive or genuinely recognize distinct individual traits.

In this particular study, the research team at IBS-CCS devised a novel behavioral paradigm utilizing mice as experimental subjects, aiming to delve deeper into their capacity for individual recognition. This innovative approach involved training the mice to associate particular individuals with rewards, subsequently monitoring their behavior when encountering the mice associated with rewards versus those without any such associations. By implementing this method, the researchers sought to gain valuable insights into the mice's ability to recognize and differentiate between individual conspecifics.

More specifically, the research team employed a spinning disk apparatus where two mice were immobilized and randomly presented to the subject mouse. The subject mouse relied on scent cues to recognize its neighbor. Water was provided as a reward to the subject mouse when it licked in response to the neighbor mouse associated with a reward, while no reward was given for licking in response to the other mouse. The objective was to assess whether the subject mouse could successfully discriminate between different individuals. Additionally, the researchers analyzed the activity of brain cells during the experiment to gain insights into the neural mechanisms involved in individual recognition.

The stimulus mice utilized in the spinning disk setup were male littermates, and the subject mice had prior familiarity with these stimulus mice. Consequently, the subject mice were able to differentiate between the stimulus mice based solely on their unique characteristics. This aspect of the experimental design suggests a high degree of reliability in the obtained results. By ensuring that the subject mice were already acquainted with the stimulus mice, any discrimination observed can be attributed to the specific individual traits of the stimulus mice rather than unfamiliarity or novelty factors.

Through the implementation of this behavioral paradigm, the researchers effectively established the crucial involvement of the dorsal CA1 region of the hippocampus in individual recognition. Notably, when the CA1 region was suppressed using a neuroinhibitor, the subject mouse exhibited an inability to differentiate its neighbor. Additionally, the IBS-CCS team employed a two-photon imaging technique enabling real-time observation of neural cell activity within the deep brain regions. This advanced imaging technique facilitated the identification of specific neuronal cells within the hippocampal CA1 region that were responsible for recognizing individual mice. By linking the functional manipulation of the CA1 region with the observed changes in neural cell activity, the researchers solidified the role of this brain region in individual recognition processes.

This finding was a notable extension of prior research, which has suggested that the dorsal CA2 region of the hippocampus is the key brain region for social memory, while indicating that the dorsal CA1 region lacks a substantial role.

In the past, scientists held the belief that social memories in rodents were transient, with no capacity for long-term memory formation regarding individual subjects. Nevertheless, the recent study conducted by the IBS-CCS has conclusively shown that mice are capable of forming enduring, long-term memories about specific individuals. This groundbreaking research challenges the previous notion and highlights the remarkable ability of mice to retain memories of individual subjects over extended periods.

According to Dr. Lee Doyun, the lead researcher of this study, the team has achieved a groundbreaking revelation by unveiling how our brains encode and retain value-based information about others, acquired through positive or negative interactions. This discovery holds profound significance as it sheds light on the intricate role our brains play in forming and nurturing human relationships through diverse social exchanges. Dr. Lee's statement underscores the study's contribution towards a deeper understanding of the neural mechanisms underlying social interactions and their impact on the development of interpersonal connections.

Moreover, the research team has made an additional discovery regarding the existence of distinct neurons within the hippocampal CA1 region of the subject mouse. These neurons are responsible for processing positive information linked to various individual mice. This finding highlights an integral aspect of social relationship formation, which involves attributing positive or negative value to social interactions with others and subsequently updating that valuation. For instance, when establishing a friendship with a specific individual, it becomes crucial to evaluate the degree of enjoyment and reward derived from engaging with them.

The identified CA1 neurons displayed a heightened response when the subject mouse encountered individuals associated with rewards. Notably, this specific response linked to reward expectations was not observed when the subject mouse was exposed to odors unrelated to social interactions, such as citral or butanol. These findings strongly suggest that the hippocampal CA1 region plays a pivotal and selective role in the establishment of associative social memories. The results imply that this brain region is specifically involved in encoding and storing information related to social interactions that are associated with positive outcomes.

The aspiration is that this newfound revelation may ultimately offer a viable remedy for diverse brain disorders that impede the ability to establish social connections.

Dr. Lee highlights that their findings hold the potential to contribute towards comprehending and suggesting therapeutic approaches for mental disorders like autism. These conditions often manifest irregularities in brain functions associated with memory processing and the comprehension of information pertaining to others. By leveraging the insights gained from their research, Dr. Lee suggests that their results could be utilized to develop effective treatment methods tailored to address such cognitive abnormalities in mental disorders.

Journal Link: Nature Communications