Title: Social Familiarity and Recollection in the CA2 region of the Hippocampus
Description: Memory is the basis of all complex social relationships. In the brain, the hippocampus is a structure that is critical for remembering interactions with, and information about, other individuals; in other words, it is critical for social recognition memory. Social memory consists of two related processes: the general sense of whether and to what extent one has previously encountered another individual (familiarity) and the specific recall of details or episodes that involve another individual (recollection). It remains controversial whether the hippocampus contributes to one or to both of these processes. Teasing out the role of the hippocampus in the different components of memory is challenging because it is not a homogenous structure but rather consists of many subpopulations of neurons that are specifically organized along its various axes. Broadly, the hippocampus is divided into the Cornu Ammonis subfields (CA1, CA2, and CA3), as well as the dentate gyrus. In addition to these subfields, the hippocampus demonstrates remarkable variation in neural and functional properties along the dorsoventral axis.

The past decade has revealed that the dorsal CA2 (dCA2) subfield is particularly important for social recognition memory. Although dCA2 has been shown to respond to and represent social information, it remains unclear as to whether it contributes to both familiarity and recollection processing. In my thesis, I address the nature of CA2 social coding using large-scale optical imaging of calcium activity in hundreds to thousands of pyramidal neurons selectively targeted within dCA2. Through intensive decoding and cross-condition analysis, my studies reveal that dCA2 contributes to the classification of novel from familiar individuals in a way that is separate from their identity, thus demonstrating familiarity processing in this region. In addition, I show that dCA2 neural activity can discern the identities of individuals with the same degree or novelty or familiarity, necessary to support recollection. Extended familiarization decreases the extent that neural activity in dCA2 generalizes across changes in context, enhancing social-spatial discrimination at the expense of generalization.

While the role of dCA2 in social memory is clear, next to nothing is known about the ventral portion of this structure (vCA2); indeed, its very existence is controversial. In my efforts to understand the role of CA2 in familiarity and recollection processing, I investigated the structure and function of CA2 in the ventral hippocampus, a region generally implicated in regulating emotion, stress, and affect. My results indicate that vCA2 is a well-defined region with characteristic morphological, electrophysiological, and molecular properties in common with dCA2. However, vCA2 also shows differences in expression of certain proteins characteristic of dCA2. Notably, and dissimilar to its dorsal counterpart, this region is defined by at least two distinct populations of neurons defined by differences in molecular expression. In contrast to the importance of dCA2 in social memory, inhibition of one of the vCA2 populations did not alter social recognition memory. Although the functional role of these populations remains elusive, I found that vCA2 activity, as measured by c-Fos activation, is significantly and selectively modulated following acute social defeat, thus providing a potential novel role for CA2 in responses to social stress.