8782 • The Journal of Neuroscience, November 11, 2020 • 40(46):8782–8798 Viewpoints Linking Social Cognition to Learning and Memory Heloise Leblanc1,2 and Steve Ramirez1,3,4,5 1Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts, 02119, 2Boston University School of Medicine, Boston, Massachusetts, 02118, 3Department of Biomedical Engineering, Boston University, Boston, Massachusetts, 02119, 4Neurophotonics Center at Boston University, Boston, Massachusetts, 02119, and 5Center for Systems Neuroscience at Boston University, Boston, Massachusetts, 02119 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 encounters facilitate new learning and help modify preexisting memories throughout the lifespan of an organism. Moreover, social encounters can help buffer stress or the effects of negative memories, as well as extinguish maladaptive behaviors. Given the importance of such interactions, there has been increasing work studying social learning and applying its concepts in a wide range of fields, including psycho- therapy and medical sociology. The process of social learning, including its neural and behavioral mechanisms, has also been a rapidly growing field of interest in neuroscience. However, the term “social learning” has been loosely applied to a variety of psychological phenomena, often without clear definition or delineations. Therefore, this review gives a definition for spe- cific aspects of social learning, provides an overview of previous work at the circuit, systems, and behavioral levels, and finally, introduces new findings on the social modulation of learning. We contextualize such social processes in the brain both through the role of the hippocampus and its capacity to process “social engrams” as well as through the brainwide real- ization of social experiences. With the integration of new technologies, such as optogenetics, chemogenetics, and calcium imaging, manipulating social engrams will likely offer a novel therapeutic target to enhance the positive buffering effects of social experiences or to inhibit fear-inducing social stimuli in models of anxiety and post-traumatic stress disorder. Key words: behavior; engram; learning; memory; optogenetics; social Introduction and Galef, 1988; Zentall, 2006).Inthisreview,webeginwiththe “ ” Social learning involves at least two agents, at least one of which notion of a social engram and propose the concept as a unifying updates their knowledge base by acquiring information from the theme across studies seeking to understand the physical basis of other (for details, see Box 1). Classifications of social learning complex cognition and behavior. In particular, we focus on recent and cognition are wide-ranging and divisive, often dependent on research that illuminates the critical role of the hippocampus in the specialty of the researchers defining the behaviors and their social cognition in rodents and humans, especially with regard to opinions regarding the presence of higher-order animal cogni- areas, such as CA2, which plays a critical role in connecting social tion in nonhuman species (Zentall and Galef, 1988; Choleris and behaviors and general mnemonic outputs. In the next section, we Kavaliers, 1999; Lacey and Solomon, 2003; Zentall, 2006; Olsson overview social learning and acquisition of memory and discuss and Phelps, 2007; Wolff, 2007; Christov-Moore et al., 2014; the social modulation of instrumental and skilled actions, spatial Gariépy et al., 2014; Keum and Shin, 2016, 2019; Debiec and tasks, and food preference. Through the lens of these types of Olsson, 2017; Kiyokawa and Hennessy, 2018; Morozov, 2018; social learning, we highlight how factors, such as the sex of a Sivaselvachandran et al., 2018; Carcea and Froemke, 2019). How learner or familiarity of a conspecific, can directly affect learning social learning in rodents can be classified per se is outside the curves. We then examine how these factors relate to the fact that focus of this review and is further discussed elsewhere (Zentall many pathways necessary and sufficient for social cognition coin- cide with general learning pathways. Finally, we transition to the social modulation of learning and memory, and how social stim- Received May 22, 2020; revised Sep. 30, 2020; accepted Oct. 2, 2020. uli, especially those of familiar individuals, can suppress or Author contributions: H.L. and S.R. wrote the paper. H.L. and S.R. edited and commented on the enhance a variety of fear responses in rodents. By deconstructing manuscript. ’ This work was supported by National Institutes of Health Early Independence Award DP5 OD023106-01, social learning s neural and behavioral mechanisms, we may de- Transformative R01, Brain and Behavior Research Foundation Young Investigator Grant, Society of Fellows at velop novel strategies that further leverage social influences as pu- Harvard University Milton Grant, Ludwig Family Foundation Grant, and McKnight Foundation Memory and tative therapeutic interventions. Cognitive Disorders Award. We thank Abby Finkelstein for exceptional mentorship, extensive comments and help with editing the manuscript, and intellectual feedback on all stages of manuscript preparation. The authors declare no competing financial interests. The Hippocampus and the Social Engram Correspondence should be addressed to Steve Ramirez at [email protected]. “ ” https://doi.org/10.1523/JNEUROSCI.1280-20.2020 The term engram, the enduring structural and functional man- Copyright © 2020 The authors ifestation of a memory, was coined .100 years ago (Schacter et Leblanc and Ramirez · Linking Social Cognition to Learning and Memory J. Neurosci., November 11, 2020 • 40(46):8782–8798 • 8783 al., 1978; Josselyn and Tonegawa, 2020). Recently, the engram lit- the nucleus accumbens was necessary for social discrimination. erature has experienced a resurgence in light of new imaging and New discoveries about the social engram ensued, and suggested molecular techniques that view and manipulate neural ensembles a pathway for social recognition memory involving the olfactory involved in contextual and emotional memory with unprece- system (Matochik, 1988; Kiyokawa et al., 2012), dorsal CA2 dented spatial-temporal resolution. In rodent models, for over a (Dudek et al., 2016; Mitre et al., 2016; A. S. Smith et al., 2016; decade, a rich body of work has focused specifically on the for- Meira et al., 2018), ventral CA1 (Dudek et al., 2016; Mitre et al., mation and retrieval of fear engrams (S. Ramirez et al., 2015; 2016; A. S. Smith et al., 2016; Meira et al., 2018), and nucleus Denny et al., 2017; Josselyn and Tonegawa, 2020). The behav- accumbens (Okuyama et al., 2016; Okuyama, 2018), as well as ioral manifestations of fear in rodents can be quantified through modulatory roles for the mPFC (Tanimizu et al., 2017; Gutzeit et a battery of outputs, including freezing, which offers a robust be- al., 2020), ACC (Tanimizu et al., 2017), amygdala (Tanimizu et havioral readout that can also be manipulated and studied at the al., 2017; Fernández et al., 2018), lateral septum (Fernández et al., cellular level. In response to such groundbreaking advances, 2018), and hypothalamus (Dudeketal.,2016; Mitre et al., 2016; more researchers have begun to investigate complex, multimodal A. S. Smith et al., 2016). behaviors, such as sociality. The co-occurrence of fear and social behaviors has become of particular interest as it has implications CA2: the black box of the hippocampus for many psychiatric disorders, including social anxiety, phobias, The central role of the hippocampus in learning and memory and post-traumatic stress disorder (PTSD) (Storm and Tecott, was historically centered around the influential concept of a “tri- 2005; Charuvastra and Cloitre, 2008; Flinn et al., 2011). synaptic pathway” defined by three main subregions: CA1, CA3, and the dentate gyrus (CA4/DG) (Teyler and Discenna, 1984; Box 1. Social learning was defined by Conte and Langston et al., 2010; Dudek et al., 2016; Tzakis and Holahan, Paolucci (2001) as a “phenomenon by means of which a 2019). Through lesions, electrophysiology, calcium imaging, and given agent (the learning agent) updates its own knowl- optogenetic studies, the roles of these subregions were often edge base (adding to, or removing from it a given infor- rigidly defined: CA1 was proposed to specialize in processing the mation, or modifying an existing representation) by spatiotemporal components of memory, CA3’s functions perceiving the positive or negative effects of any given included pattern completion and rapid, one-trial encoding, and event undergone or actively produced by another agent the DG’s functions involved pattern separation and orthogonal- on a state of the world which the learning agent has as a izing inputs to discrete populations of cells (Teyler and goal.” Specifically, there exist at least two types of social Discenna, 1984; Kesner et al., 2004; Langston et al., 2010). learning: facilitation and imitation. Facilitation involves Although defined as early as 1934 by Rafael Lorente de Nó, CA2 observing the features and behaviors of a social