Sickness and the social brain: How the immune system regulates behavior across species

2021 ◽  
Author(s):  
Benjamin A. Devlin ◽  
Caroline J. Smith ◽  
Staci D. Bilbo
Keyword(s):  
Immune System ◽  
Social Behavior ◽  
Brain Regions ◽  
Behavior Changes ◽  
Social Brain ◽  
Evolutionary Origins ◽  
Immune Mediators ◽  
The Social ◽  
Sickness Behaviors ◽  
The Brain

Many instances of sickness critically involve the immune system. The immune system talks to the brain in a bi-directional loop. This discourse affords the immune system immense control, such that it can influence behavior and optimize recovery from illness. These behavioral responses to infection are called sickness behaviors and can manifest in many ways, including changes in mood, motivation, or energy. Fascinatingly, most of these changes are conserved across species, and most organisms demonstrate some form of sickness behaviors. One of the most interesting sickness behaviors, and not immediately obvious, is altered sociability. Here, we discuss how the immune system impacts social behavior, by examining the brain regions and immune mediators involved in this process. We first outline how social behavior changes in response to infection in various species. Next, we explore which brain regions control social behavior and their evolutionary origins. Finally, we describe which immune mediators establish the link between illness and social behavior, in the context of both normal development and infection. Overall, we hope to make clear the striking similarities between the mechanisms that facilitate changes in sociability in derived and ancestral vertebrate, as well as invertebrate, species.

scholarly journals Cerebellar modulation of the reward circuitry and social behavior

Science ◽  
2019 ◽  
Vol 363 (6424) ◽  
pp. eaav0581 ◽  
Author(s):  
Ilaria Carta ◽  
Christopher H. Chen ◽  
Amanda L. Schott ◽  
Schnaude Dorizan ◽  
Kamran Khodakhah
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Mental Disorders ◽  
Ventral Tegmental Area ◽  
Social Preference ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Reward Circuitry ◽  
The Social ◽  
The Brain

The cerebellum has been implicated in a number of nonmotor mental disorders such as autism spectrum disorder, schizophrenia, and addiction. However, its contribution to these disorders is not well understood. In mice, we found that the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward. Optogenetic activation of the cerebello-VTA projections was rewarding and, in a three-chamber social task, these projections were more active when the animal explored the social chamber. Intriguingly, activity in the cerebello-VTA pathway was required for the mice to show social preference in this task. Our data delineate a major, previously unappreciated role for the cerebellum in controlling the reward circuitry and social behavior.

scholarly journals From Hyposociability to Hypersociability—The Effects of PSD-95 Deficiency on the Dysfunctional Development of Social Behavior

2021 ◽  
Vol 15 ◽  
Author(s):  
Wen-Jun Gao ◽  
Nancy R. Mack
Keyword(s):  
Social Behavior ◽  
Adult Development ◽  
Ampa Receptors ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Scaffolding Protein ◽  
Excitatory Synapses ◽  
Social Brain ◽  
Functional Maturation ◽  
The Social

Abnormal social behavior, including both hypo- and hypersociability, is often observed in neurodevelopmental disorders such as autism spectrum disorders. However, the mechanisms associated with these two distinct social behavior abnormalities remain unknown. Postsynaptic density protein-95 (PSD-95) is a highly abundant scaffolding protein in the excitatory synapses and an essential regulator of synaptic maturation by binding to NMDA and AMPA receptors. The DLG4 gene encodes PSD-95, and it is a risk gene for hypersocial behavior. Interestingly, PSD-95 knockout mice exhibit hyposociability during adolescence but hypersociability in adulthood. The adolescent hyposociability is accompanied with an NMDAR hyperfunction in the medial prefrontal cortex (mPFC), an essential part of the social brain for control of sociability. The maturation of mPFC development is delayed until young adults. However, how PSD-95 deficiency affects the functional maturation of mPFC and its connection with other social brain regions remains uncharacterized. It is especially unknown how PSD-95 knockout drives the switch of social behavior from hypo- to hyper-sociability during adolescent-to-adult development. We propose an NMDAR-dependent developmental switch of hypo- to hyper-sociability. PSD-95 deficiency disrupts NMDAR-mediated synaptic connectivity of mPFC and social brain during development in an age- and pathway-specific manner. By utilizing the PSD-95 deficiency mouse, the mechanisms contributing to both hypo- and hyper-sociability can be studied in the same model. This will allow us to assess both local and long-range connectivity of mPFC and examine how they are involved in the distinct impairments in social behavior and how changes in these connections may mature over time.

scholarly journals Seven Computations of the Social Brain

2021 ◽  
Author(s):  
Tanaz Molapour ◽  
Cindy C Hagan ◽  
Brian Silston ◽  
Haiyan Wu ◽  
Maxwell Ramstead ◽  
...  
Keyword(s):  
Social Interactions ◽  
Social World ◽  
Social Brain ◽  
Verbal Cues ◽  
True Nature ◽  
Multiple Modalities ◽  
The Social ◽  
Processing Demands ◽  
Social Signaling ◽  
The Brain

ABSTRACT The social environment presents the human brain with the most complex of information processing demands. The computations that the brain must perform occur in parallel, combine social and nonsocial cues, produce verbal and non-verbal signals, and involve multiple cognitive systems; including memory, attention, emotion, learning. This occurs dynamically and at timescales ranging from milliseconds to years. Here, we propose that during social interactions, seven core operations interact to underwrite coherent social functioning; these operations accumulate evidence efficiently – from multiple modalities – when inferring what to do next. We deconstruct the social brain and outline the key components entailed for successful human social interaction. These include (1) social perception; (2) social inferences, such as mentalizing; (3) social learning; (4) social signaling through verbal and non-verbal cues; (5) social drives (e.g., how to increase one’s status); (6) determining the social identity of agents, including oneself; and (7) minimizing uncertainty within the current social context by integrating sensory signals and inferences. We argue that while it is important to examine these distinct aspects of social inference, to understand the true nature of the human social brain, we must also explain how the brain integrates information from the social world.

scholarly journals The social brain in female autism: a structural imaging study of twins

2020 ◽  
Vol 15 (4) ◽  
pp. 423-436
Author(s):  
Élodie Cauvet ◽  
Annelies van’t Westeinde ◽  
Roberto Toro ◽  
Ralf Kuja-Halkola ◽  
Janina Neufeld ◽  
...  
Keyword(s):  
Sex Differences ◽  
Social Cognition ◽  
Brain Structure ◽  
Imaging Study ◽  
Autistic Traits ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Social Brain ◽  
Twin Design ◽  
The Social

Abstract A female advantage in social cognition (SoC) might contribute to women’s underrepresentation in autism spectrum disorder (ASD). The latter could be underpinned by sex differences in social brain structure. This study investigated the relationship between structural social brain networks and SoC in females and males in relation to ASD and autistic traits in twins. We used a co-twin design in 77 twin pairs (39 female) aged 12.5 to 31.0 years. Twin pairs were discordant or concordant for ASD or autistic traits, discordant or concordant for other neurodevelopmental disorders or concordant for neurotypical development. They underwent structural magnetic resonance imaging and were assessed for SoC using the naturalistic Movie for the Assessment of Social Cognition. Autistic traits predicted reduced SoC capacities predominantly in male twins, despite a comparable extent of autistic traits in each sex, although the association between SoC and autistic traits did not differ significantly between the sexes. Consistently, within-pair associations between SoC and social brain structure revealed that lower SoC ability was associated with increased cortical thickness of several brain regions, particularly in males. Our findings confirm the notion that sex differences in SoC in association with ASD are underpinned by sex differences in brain structure.

scholarly journals The Legacy of Sickness Behaviors

2020 ◽  
Vol 11 ◽  
Author(s):  
Keith W. Kelley ◽  
Stephen Kent
Keyword(s):  
Immune System ◽  
Body Temperature ◽  
Communication Systems ◽  
Memory Deficits ◽  
Sleep Disruption ◽  
Sickness Behaviors ◽  
Systemic Infections ◽  
The Brain ◽  
Conceptual Advance

Systemic infections of all types lead to a syndrome known as sickness behaviors. Changes in the behavior of febrile humans and animals formed the original basis for this concept. Body temperature is behaviorally regulated in both endotherms and ectotherms. However, infections cause other changes in body functions, including sleep disruption, anorexia, cognitive and memory deficits and disorientation. The brain mediates this entire cluster of symptoms, even though most major infections occur outside the brain. The true importance of sickness behaviors is not the numerous discoveries of symptoms that affect all of us when we get sick. Instead, the legacy of 30 years of research in sickness behaviors is that it established the physiologic importance of reciprocal communication systems between the immune system and the brain. This conceptual advance remains in its infancy.

scholarly journals Immune System in the Brain: A Modulatory Role on Dendritic Spine Morphophysiology?

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Oscar Kurt Bitzer-Quintero ◽  
Ignacio González-Burgos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Dendritic Spines ◽  
Cell Lineage ◽  
Myeloid Cell ◽  
Brain Parenchyma ◽  
Immune Mediators ◽  
The Central Nervous System ◽  
The Brain

The central nervous system is closely linked to the immune system at several levels. The brain parenchyma is separated from the periphery by the blood brain barrier, which under normal conditions prevents the entry of mediators such as activated leukocytes, antibodies, complement factors, and cytokines. The myeloid cell lineage plays a crucial role in the development of immune responses at the central level, and it comprises two main subtypes: (1) resident microglia, distributed throughout the brain parenchyma; (2) perivascular macrophages located in the brain capillaries of the basal lamina and the choroid plexus. In addition, astrocytes, oligodendrocytes, endothelial cells, and, to a lesser extent, neurons are implicated in the immune response in the central nervous system. By modulating synaptogenesis, microglia are most specifically involved in restoring neuronal connectivity following injury. These cells release immune mediators, such as cytokines, that modulate synaptic transmission and that alter the morphology of dendritic spines during the inflammatory process following injury. Thus, the expression and release of immune mediators in the brain parenchyma are closely linked to plastic morphophysiological changes in neuronal dendritic spines. Based on these observations, it has been proposed that these immune mediators are also implicated in learning and memory processes.

scholarly journals Abnormal social behaviors and dysfunction of autism-related genes associated with daily agonistic interactions in mice

2017 ◽  
Author(s):  
Natalia N. Kudryavtseva ◽  
Irina L. Kovalenko ◽  
Dmitry A. Smagin ◽  
Anna G. Galyamina ◽  
Vladimir N. Babenko
Keyword(s):  
Social Behavior ◽  
Social Environment ◽  
Social Behaviors ◽  
Brain Regions ◽  
Autistic Spectrum Disorders ◽  
Male Mice ◽  
Agonistic Interactions ◽  
Autistic Spectrum ◽  
Spectrum Disorders ◽  
The Brain

AbstractBackgroundThe ability of people to communicate with each other is a necessary component of social behavior and the normal development of individuals who live in a community. An apparent decline in sociability may be the result of a negative social environment or the development of affective and neurological disorders, including autistic spectrum disorders. The behavior of these humans may be characterized by the deterioration of socialization, low communication, and repetitive and restricted behaviors. This study aimed to analyze changes in the social behaviors of male mice induced by daily agonistic interactions and investigate the involvement of genes, related with autistic spectrum disorders in the process of the impairment of social behaviors.MethodsAbnormal social behavior is induced by repeated experiences of aggression accompanied by wins (winners) or chronic social defeats (losers) in daily agonistic interactions in male mice. The collected brain regions (the midbrain raphe nuclei, ventral tegmental area, striatum, hippocampus, and hypothalamus) were sequenced at JSC Genoanalytica (http://genoanalytica.ru/, Moscow, Russia). The Cufflinks program was used to estimate the gene expression levels. Bioinformatic methods were used for the analysis of differentially expressed genes in male mice.ResultsThe losers exhibited an avoidance of social contacts toward unfamiliar conspecific, immobility and low communication on neutral territory. The winners demonstrated aggression and hyperactivity in this condition. The exploratory activity (rearing) and approaching behavior time towards the partner were decreased, and the number of episodes of repetitive self-grooming behavior was increased in both social groups. These symptoms were similar to the symptoms observed in animal models of autistic spectrum disorders. In an analysis of the RNA-Seq database of the whole transcriptome in the brain regions of the winners and losers, we identified changes in the expression of the following genes, which are associated with autism in humans: Tph2, Maoa, Slc6a4, Htr7,Gabrb3, Nrxn1, Nrxn2, Nlgn1, Nlgn2, Nlgn3, Shank2, Shank3, Fmr1, Ube3a, Pten, Cntn3, Foxp2, Oxtr, Reln, Cadps2, Pcdh10, Ctnnd2, En2, Arx, Auts2, Mecp2, and Ptchd1.Common and specific changes in the expression of these genes in different brain regions were identified in the winners and losers.ConclusionsThis research demonstrates for the first time that abnormalities in social behaviors that develop under a negative social environment in adults may be associated with alterations in expression of genes, related with autism in the brain.

scholarly journals Distinct neural mechanisms of social orienting and mentalizing revealed by independent measures of neural and eye movement typicality

2019 ◽  
Author(s):  
Michal Ramot ◽  
Catherine Walsh ◽  
Gabrielle E. Reimann ◽  
Alex Martin
Keyword(s):  
Eye Movement ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Extensive Study ◽  
Neural Systems ◽  
Typically Developing ◽  
Social Brain ◽  
Social Orienting ◽  
The Social ◽  
Interacting Systems

AbstractExtensive study of typically developing individuals and those on the autism spectrum has identified a large number of brain regions associated with our ability to navigate the social world. Although it is widely appreciated that this so-called ‘social brain’ is composed of distinct, interacting systems, these component parts have yet to be clearly elucidated. Here we used measures of eye movement and neural typicality – based on the degree to which subjects deviated from the norm – while typically developing (N = 62) and individuals with autism (N = 36) watched a large battery of movies depicting social interactions. Our findings provide clear evidence for distinct, but overlapping, neural systems underpinning two major components of the ‘social brain’, social orienting and inferring the mental state of others.

scholarly journals Self-other representation in the social brain reflects social connection

2019 ◽  
Author(s):  
Andrea L. Courtney ◽  
Meghan L. Meyer
Keyword(s):  
Social Network ◽  
Well Being ◽  
The Self ◽  
Social Connection ◽  
Social Categories ◽  
Social Brain ◽  
Self And Other ◽  
Neural Representations ◽  
The Social ◽  
The Brain

Social connection is critical to well-being, yet how the brain reflects our attachment to other people remains largely unknown. We combined univariate and multivariate brain imaging analyses to assess whether and how the brain organizes representations of others based on how connected they are to our own identity. During an fMRI scan, participants (N=43) completed a self- and other-reflection task for 16 targets: the self, five close others, five acquaintances, and five celebrities. In addition, they reported their subjective closeness to each target and their own trait loneliness. We examined neural responses to the self and others in a brain region that has been associated with self-representation (medial prefrontal cortex; MPFC) and across the whole brain. The structure of self-other representation in the MPFC and across the social brain appeared to cluster targets into three social categories: the self, social network members (including close others and acquaintances), and celebrities. Moreover, both univariate activation in MPFC and multivariate self-other similarity in MPFC and across the social brain increased with subjective self-other closeness ratings. Critically, participants who were less socially connected (i.e. lonelier) showed altered self-other mapping in social brain regions. Most notably, in MPFC, loneliness was associated with reduced representational similarity between the self and others. The social brain apparently maintains information about broad social categories as well as closeness to the self. Moreover, these results point to the possibility that feelings of chronic social disconnection may be mirrored by a ‘lonelier’ neural self-representation.Significance StatementSocial connection is critical to well-being, yet how the brain reflects our attachment to people remains unclear. We found that the social brain stratifies neural representations of people based on our subjective connection to them, separately clustering people who are and are not in our social network. Moreover, the people we feel closest to are represented most closely to ourselves. Finally, lonelier individuals also appeared to have a ‘lonelier’ neural self-representation in the MPFC, as loneliness attenuated the closeness between self and other neural representations in this region. The social brain appears to map our interpersonal ties, and alterations in this map may help explain why lonely individuals endorse statements such as ‘people are around me but not with me’.

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