Prosocial Learning and Motivation across the Lifespan

2024 BACN Early-Career Prize Lecture Many of our decisions affect other people. Our choices can decelerate climate change, stop the spread of infectious diseases, and directly help or harm others. Prosocial behaviours – decisions that help others – could contribute to reducing the impact of these challenges, yet their computational and neural mechanisms remain poorly understood. I will present recent work that examines prosocial motivation, how willing we are to incur costs to help others, prosocial learning, how we learn from the outcomes of our choices when they affect other people, and prosocial preferences, our self-reports of helping others. Throughout the talk, I will outline the possible computational and neural bases of these behaviours, and how they may differ from young adulthood to old age.

From pecking order to ketamine - neural mechanism of social and emotional behavior

Emotions and social interactions color our lives and shape our behaviors. Using animal models and engineered manipulations, we aim to understand how social and emotional behaviors are encoded in the brain, focusing on the neural circuits underlying dominance hierarchy and depression. This lecture will highlight our recent discoveries on how downward social mobility leads to depression; how ketamine tames depression by blocking burst firing in the brain’s antireward center; and, how glia-neuron interaction plays a surprising role in this process. I will also present our recent work on the mechanism underlying the sustained antidepressant activity of ketamine and its brain region specificity. With these results, we hope to illuminate on a more unified theory on ketamine’s mode of action and inspire new treatment strategies for depression.

From pecking order to ketamine - neural mechanism of social and emotional behavior

Emotions and social interactions color our lives and shape our behaviors. Using animal models and engineered manipulations, we aim to understand how social and emotional behaviors are encoded in the brain, focusing on the neural circuits underlying dominance hierarchy and depression. This lecture will highlight our recent discoveries on how downward social mobility leads to depression; how ketamine tames depression by blocking burst firing in the brain’s antireward center; and, how glia-neuron interaction plays a surprising role in this process. I will also present our recent work on the mechanism underlying the sustained antidepressant activity of ketamine and its brain region specificity. With these results, we hope to illuminate on a more unified theory on ketamine’s mode of action and inspire new treatment strategies for depression.

Microbial modulation of zebrafish behavior and brain development

There is growing recognition that host-associated microbiotas modulate intrinsic neurodevelopmental programs including those underlying human social behavior. Despite this awareness, the fundamental processes are generally not understood. We discovered that the zebrafish microbiota is necessary for normal social behavior. By examining neuronal correlates of behavior, we found that the microbiota restrains neurite complexity and targeting of key forebrain neurons within the social behavior circuitry. The microbiota is also necessary for both localization and molecular functions of forebrain microglia, brain-resident phagocytes that remodel neuronal arbors. In particular, the microbiota promotes expression of complement signaling pathway components important for synapse remodeling. Our work provides evidence that the microbiota modulates zebrafish social behavior by stimulating microglial remodeling of forebrain circuits during early neurodevelopment and suggests molecular pathways for therapeutic interventions during atypical neurodevelopment.

Hormonal control of brain sex differences

Social neuroscience studies of racial ingroup bias in empathy

Empathy is supposed to play a functional role in prosocial behavior. However, there has been behavioral evidence that people do not empathize everyone equally. I’ll present studies that show brain imaging evidence for racial ingroup bias in empathy for pain. These studies reveal multiple-level neural mechanisms underlying racial ingroup bias in empathy. I’ll also discuss potential intervention of racial ingroup bias in empathy and its social implications.

Brain oxytocin as a modulator of social approach versus avoidance

Translational Biomarkers in Preclinical Models of Neurodevelopmental Disorders

The effects of maternal immune activation on early development in an outbred strain of mice

SimBA for Behavioral Neuroscientists

Several excellent computational frameworks exist that enable high-throughput and consistent tracking of freely moving unmarked animals. SimBA introduce and distribute a plug-and play pipeline that enables users to use these pose-estimation approaches in combination with behavioral annotation for the generation of supervised machine-learning behavioral predictive classifiers. SimBA was developed for the analysis of complex social behaviors, but includes the flexibility for users to generate predictive classifiers across other behavioral modalities with minimal effort and no specialized computational background. SimBA has a variety of extended functions for large scale batch video pre-processing, generating descriptive statistics from movement features, and interactive modules for user-defined regions of interest and visualizing classification probabilities and movement patterns.

Molecular, receptor, and neural bases for chemosensory-mediated sexual and social behavior in mice

For many animals, the sense of olfaction plays a major role in controlling sexual behaviors. Olfaction helps animals to detect mates, discriminate their status, and ultimately, decide on their behavioral output such as courtship behavior or aggression. Specific pheromone cues and receptors have provided a useful model to study how sensory inputs are converted into certain behavioral outputs. With the aid of recent advances in tools to record and manipulate genetically defined neurons, our understanding of the neural basis of sexual and social behavior has expanded substantially. I will discuss the current understanding of the neural processing of sex pheromones and the neural circuitry which controls sexual and social behaviors and ultimately reproduction, by focusing on rodent studies, mainly in mice, and the vomeronasal sensory system.

Distinct limbic-hypothalamic circuits for the generation of social behaviors

The main pillars of social behaviors involve (1) mating, where males copulate with female partners to reproduce, and (2) aggression, where males fight conspecific male competitors in territory guarding. Decades of study have identified two key regions in the hypothalamus, the medial preoptic nucleus (MPN) and the ventrolateral part of ventromedial hypothalamus (VMHvl) , that are essential for male sexual and aggressive behaviors, respectively. However, it remains ambiguous what area directs excitatory control of the hypothalamic activity and generates the initiation signal for social behaviors. Through neural tracing, in vivo optical recording and functional manipulations, we identified the estrogen receptor alpha (Esr1)-expressing cells in the posterior amygdala (PA) as a main source of excitatory inputs to the MPN and VMHvl, and key hubs in mating and fighting circuits in males. Importantly, two spatially-distinct populations in the PA regulate male sexual and aggressive behaviors, respectively. Moreover, these two subpopulations in the PA display differential molecular phenotypes, projection patterns and in vivo neural responses. Our work also observed the parallels between these social behavior circuits and basal ganglia circuits to control motivated behaviors, which Larry Swanson (2000) originally proposed based on extensive developmental and anatomical evidence.

Three levels of variability in the collective behavior of locusts

Many aspects of collective behavior depend on interactions between conspecifics. This is especially true for the collective motion of locusts, which swarm in millions while maintaining synchrony among individuals. However, whether locusts share and maintain the same socio-behavioral patterns – between groups, individuals and situations – remains an open question. Studying marching locusts under lab conditions, we found that (1) different groups behave differently; (2) locusts within a group homogenize their behavior; and (3) individuals have different socio-behavioral tendencies and context-dependent states. These variability levels suggest that behavioral differences within and among individuals exist, affect others, and shape the collective behavior of the entire group.

Generating and personalizing social behavior

Dr. Stowers obtained her PhD at Harvard University and remained there to undertake the study of olfactory-mediated behavior with Catherine Dulac. During this time she completed experiments identifying vomeronasal organ neurons as sensors for mouse pheromones. In 2002 she began independent work at The Scripps Research Institute where she remains today. Her lab is leveraging the olfactory system to identify and study the information code that underlies emotion-linked innate behavior. She has been a Pew Scholar and a Senior Scholar in Neuroscience from the Ellison Medical Foundation.

The neuroecological context of group living

Dr. Sean O'Donnell is a Professor of Biodiversity Earth & Environmental Science at Drexel University, USA. His neuroscience research focuses on how brain structure plasticity & evolution are affected by social behavior, mainly using insects as models. He is also interested in tropical ecology & thermal physiology. He conducts field research & teaches field courses in Central & South America, as well as in the Negev Desert in Israel.

Hypothalamic control of internal states underlying social behaviors in mice

Social interactions such as mating and fighting are driven by internal emotional states. How can we study internal states of an animal when it cannot tell us its subjective feelings? Especially when the meaning of the animal’s behavior is not clear to us, can we understand the underlying internal states of the animal? In this talk, I will introduce our recent work in which we used male mounting behavior in mice as an example to understand the underlying internal state of the animals. In many animal species, males exhibit mounting behavior toward females as part of the mating behavior repertoire. Interestingly, males also frequently show mounting behavior toward other males of the same species. It is not clear what the underlying motivation is - whether it is reproductive in nature or something distinct. Through detailed analysis of video and audio recordings during social interactions, we found that while male-directed and female-directed mounting behaviors are motorically similar, they can be distinguished by both the presence of ultrasonic vocalization during female-directed mounting (reproductive mounting) and the display of aggression following male-directed mounting (aggressive mounting). Using optogenetics, we further identified genetically defined neural populations in the medial preoptic area (MPOA) that mediate reproductive mounting and the ventrolateral ventromedial hypothalamus (VMHvl) that mediate aggressive mounting. In vivo microendocsopic imaging in MPOA and VMHvl revealed distinct neural ensembles that mainly encode either a reproductive or an aggressive state during which male or female directed mounting occurs. Together, these findings demonstrate that internal states are represented in the hypothalamus and that motorically similar behaviors exhibited under different contexts may reflect distinct internal states.

Anterior Cingulate inputs to nucleus accumbens control the social transfer of pain and analgesia

Empathy plays a critical role in social interactions, and many species, including rodents, display evolutionarily conserved behavioral antecedents of empathy. In both humans and rodents, the anterior cingulate cortex (ACC) encodes information about the affective state of others. However, little is known about which downstream targets of the ACC contribute to empathy behaviors. We optimized a protocol for the social transfer of pain behavior in mice and compared the ACC-dependent neural circuitry responsible for this behavior with the neural circuitry required for the social transfer of two related states: analgesia and fear. We found that a 1-hour social interaction between a bystander mouse and a cagemate experiencing inflammatory pain led to congruent mechanical hyperalgesia in the bystander. This social transfer led to activation of neurons in the ACC and several downstream targets, including the nucleus accumbens (NAc), which was revealed by monosynaptic rabies virus tracing to be directly connected to the ACC. Bidirectional manipulation of activity in ACC-to-NAc inputs influenced the acquisition of socially transferred pain. Further, the social transfer of analgesia also depended upon ACC-NAc inputs. By contrast, the social transfer of fear instead required activity in ACC projections to the basolateral amygdala. This shows that mice rapidly adopt the sensory-affective state of a social partner, regardless of the valance of the information (pain, fear, or pain relief). We find that the ACC generates specific and appropriate empathic behavioral responses through distinct downstream targets. More sophisticated understanding of evolutionarily conserved brain mechanisms of empathy will also expedite the development of new therapies for the empathy-related deficits associated with a broad range of neuropsychiatric disorders.

Personality Evaluated: What Do Other People Really Think of You?

What do other people really think of you? In this talk, I highlight the unique perspective that other people have on the most consequential aspects of our personalities—how we treat others, our best and worst qualities, and our moral character. First, I compare how people thought they behaved with how they actually behaved in everyday life (based on observer ratings of unobtrusive audio recordings; 217 people, 2,519 observations). I show that when people think they are being kind (vs. rude), others do not necessarily agree. This suggests that people may have blind spots about how well they are treating others in the moment. Next, I compare what 463 people thought their own best and worst traits were with what their friends thought about them. The results reveal that friends are more likely to point out flaws in the prosocial and moral domains (e.g., “inconsiderate”, “selfish”, “manipulative”) than are people themselves. Does this imply that others might want us to be more moral? To find out, I compare what targets (N = 800) want to change about their own personalities with what their close others (N = 958) want to change about them. The results show that people don’t particularly want to be more moral, and their close others don’t want them to be more moral, either. I conclude with future directions on honest feedback as a pathway to self-insight and, ultimately, self-improvement.

Neural mechanisms of aggression

Aggression is an innate social behavior essential for competing for resources, securing mates, defending territory and protecting the safety of oneself and family. In the last decade, significant progress has been made towards an understanding of the neural circuit underlying aggression using a set of modern neuroscience tools. Here, I will talk about the history and recent progress in the study of aggression.

Leveraging olfaction to understand how the brain and the body generate social behavior

Courtship behavior is an innate model for many types of brain computations including sensory detection, learning and memory, and internal state modulation. Despite the robustness of the behavior, we have little understanding of the underlying neural circuits and mechanisms. The Stowers’ lab is leveraging the ability of specialized olfactory cues, pheromones, to specifically activate and therefore identify and study courtship circuits in the mouse. We are interested in identifying general circuit principles (specific brain nodes and information flow) that are common to all individuals, in order to additionally study how experience, gender, age, and internal state modulate and personalize behavior. We are solving two parallel sensory to motor courtship circuits, that promote social vocal calling and scent marking, to study information processing of behavior as a complete unit instead of restricting focus to a single brain region. We expect comparing and contrasting the coding logic of two courtship motor behaviors will begin to shed light on general principles of how the brain senses context, weighs experience and responds to internal state to ultimately decide appropriate action.

Blood is thicker than water

According to Hamilton’s inclusive fitness hypothesis, kinship is an organizing principle of social behavior. Behavioral evidence supporting this hypothesis includes the ability to recognize kin and the adjustment of behavior based on kin preference with respect to altruism, attachment and care for offspring in insect societies. Despite the fundamental importance of kinship behavior, the underlying neural mechanisms are poorly understood. We repeated behavioral experiments by Hepper on behavioral preference of rats for their kin. Consistent with Hepper’s work, we find a developmental time course for kinship behavior, where rats prefer sibling interactions at young ages and express non-sibling preferences at older ages. In probing the brain areas responsible for this behavior, we find that aspiration lesions of the lateral septum but not control lesions of cingulate cortices eliminate the behavioral preference in young animals for their siblings and in older rats for non-siblings. We then presented awake and anaesthetized rats with odors and calls of age- and status-matched kin (siblings and mothers) and non-kin (non-siblings and non-mothers) conspecifics, while performing in vivo juxta-cellular and whole-cell patch-clamp recordings in the lateral septum. We find multisensory (olfactory and auditory) neuronal responses, whereby neurons typically responded preferentially but not exclusively to individual social stimuli. Non-kin-odor responsive neurons were found dorsally, while kin-odor responsive neurons were located in ventrally in the lateral septum. To our knowledge such an ordered representation of response preferences according to kinship has not been previously observed and we refer this organization as nepotopy. Nepotopy could be instrumental in reading out kinship from preferential but not exclusive responses and in the generation of differential behavior according to kinship. Thus, our results are consistent with a role of the lateral septum in organizing mammalian kinship behavior.

Neurobiology of Social Behavior

Social interactions are central to the human experience, yet it is also one of the faculty of the brain that is the most impaired by mental illness. Similarly, social interactions are essential for animals to survive, reproduce, and raise their young. Over the years, my lab has attempted to decipher the unique characteristics of social recognition: what are the unique cues that trigger distinct social behaviors, what is the nature and identity of social behavior circuits, how is the function of these circuits different in males and females and how are they modulated by the animal physiological status? In this lecture, I will describe our recent progress in using genetic, imaging, molecular and behavioral approaches to understand how the brain controls specific social behaviors in both males and females, and how areas throughout the brain participate in the positive and negative controls of specific social interactions. I will also describe how new approaches of single cell transcriptomics have enabled us to uncover specific cell populations involved in distinct social behaviors and the basis of their activity modulation according to the animal state.

Social reward learning: basic mechanisms and therapuetic opportunities

Analysis of anxiety-related/social behaviour and neural circuitry abnormalities in ligand of Numb protein X (LNX) knockout mice

FENS Forum 2024

Cellular and circuit underpinnings of social behaviour adaptations

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Effects of medial prefrontal cortical neurons projecting to the medial preoptic area on the social behaviour of rats

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Exploring the role of UCP2 uncoupling protein 2 (UCP2) in social behaviour through vasopressinergic pathways

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Functional mapping of brain pathways involved in the gut microbial modulation of social behaviour

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The impact of CA2 E/I imbalance on social behaviour and network activity

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NGF-sensitive interpeduncular nucleus (IPN) neurons in circuits shaping social behaviour: Anatomical and functional studies of the nucleus incertus–IPN–ventral hippocampus axis

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Novel DVC interlinking home cage monitoring system facilitates social behavioural testing in mice

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