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1.
Int J Mol Sci ; 25(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731836

ABSTRACT

The process of domestication, despite its short duration as it compared with the time scale of the natural evolutionary process, has caused rapid and substantial changes in the phenotype of domestic animal species. Nonetheless, the genetic mechanisms underlying these changes remain poorly understood. The present study deals with an analysis of the transcriptomes from four brain regions of gray rats (Rattus norvegicus), serving as an experimental model object of domestication. We compared gene expression profiles in the hypothalamus, hippocampus, periaqueductal gray matter, and the midbrain tegmental region between tame domesticated and aggressive gray rats and revealed subdivisions of differentially expressed genes by principal components analysis that explain the main part of differentially gene expression variance. Functional analysis (in the DAVID (Database for Annotation, Visualization and Integrated Discovery) Bioinformatics Resources database) of the differentially expressed genes allowed us to identify and describe the key biological processes that can participate in the formation of the different behavioral patterns seen in the two groups of gray rats. Using the STRING- DB (search tool for recurring instances of neighboring genes) web service, we built a gene association network. The genes engaged in broad network interactions have been identified. Our study offers data on the genes whose expression levels change in response to artificial selection for behavior during animal domestication.


Subject(s)
Aggression , Brain , Animals , Rats , Brain/metabolism , Aggression/physiology , Transcriptome/genetics , Principal Component Analysis , Gene Expression Profiling/methods , Behavior, Animal , Domestication , Molecular Sequence Annotation , Male , Gene Regulatory Networks , Gene Expression Regulation
2.
BMC Psychiatry ; 24(1): 335, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702695

ABSTRACT

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. METHODS: The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. RESULTS: Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. CONCLUSION: This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.


Subject(s)
Ankyrins , Kruppel-Like Transcription Factors , Polymorphism, Single Nucleotide , Humans , Male , Polymorphism, Single Nucleotide/genetics , Ankyrins/genetics , Adult , Kruppel-Like Transcription Factors/genetics , Middle Aged , Substance Withdrawal Syndrome/genetics , Substance Withdrawal Syndrome/psychology , Alcoholism/genetics , Alcoholism/psychology , Aggression/psychology , Aggression/physiology , Anxiety/genetics , Anxiety/psychology , Epistasis, Genetic , Behavioral Symptoms/genetics , Genetic Predisposition to Disease/genetics , Alleles
3.
Genesis ; 62(3): e23603, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38738564

ABSTRACT

The vomeronasal organ (VNO) is a specialized chemoreceptive structure in many vertebrates that detects chemical stimuli, mostly pheromones, which often elicit innate behaviors such as mating and aggression. Previous studies in rodents have demonstrated that chemical stimuli are actively transported to the VNO via a blood vessel-based pumping mechanism, and this pumping mechanism is necessary for vomeronasal stimulation in behaving animals. However, the molecular mechanisms that regulate the vomeronasal pump remain mostly unknown. In this study, we observed a high level of expression of phosphodiesterase 5A (PDE5A) in the vomeronasal blood vessel of mice. We provided evidence to support the potential role of PDE5A in vomeronasal pump regulation. Local application of PDE5A inhibitors-sildenafil or tadalafil-to the vomeronasal organ (VNO) reduced stimulus delivery into the VNO, decreased the pheromone-induced activity of vomeronasal sensory neurons, and attenuated male-male aggressive behaviors. PDE5A is well known to play a role in regulating blood vessel tone in several organs. Our study advances our understanding of the molecular regulation of the vomeronasal pump.


Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 5 , Vomeronasal Organ , Animals , Vomeronasal Organ/metabolism , Mice , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 5/genetics , Male , Phosphodiesterase 5 Inhibitors/pharmacology , Tadalafil/pharmacology , Sildenafil Citrate/pharmacology , Pheromones/metabolism , Aggression/physiology , Female , Mice, Inbred C57BL
4.
Sheng Li Xue Bao ; 76(2): 309-318, 2024 Apr 25.
Article in Chinese | MEDLINE | ID: mdl-38658379

ABSTRACT

Innate behavior is mainly controlled by genetics, but is also regulated by social experiences such as social isolation. Studies in animal models such as Drosophila and mice have found that social isolation can regulate innate behaviors through the changes at the molecular level, such as hormone, neurotransmitter, neuropeptide level, and at the level of neural circuits. In this review, we summarized the research progress on the regulation of social isolation on various animal innate behaviors, such as sleep, reproduction and aggression by altering the expression of conserved neuropeptides and neurotransmitters, hoping to deepen the understanding of the key and conserved signal pathways that regulate innate behavior by social isolation.


Subject(s)
Neuropeptides , Social Isolation , Animals , Neuropeptides/physiology , Neuropeptides/metabolism , Behavior, Animal/physiology , Mice , Instinct , Sleep/physiology , Aggression/physiology , Humans , Reproduction/physiology , Neurotransmitter Agents/physiology , Neurotransmitter Agents/metabolism
5.
Neuropharmacology ; 252: 109949, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38636726

ABSTRACT

Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A receptor partial agonist, decreases stress-related behavior in male mice exposed to repeated social aggression. Additionally, we explored the likelihood that these behavioral changes are related to anti-inflammatory properties of [(R)-DOI]. Animals were subjected to the Stress Alternatives Model (SAM), an escapable social stress paradigm in which animals develop reactive coping strategies - remaining in the SAM arena (Stay) with a social aggressor, or dynamically initiated stress coping strategies that involve utilizing the escape holes (Escape) to avoid aggression. Mice expressing these behavioral phenotypes display behaviors like those in other social aggression models that separate animals into stress-vulnerable (as for Stay) or stress-resilient (as for Escape) groups, which have been shown to have distinct inflammatory responses to social stress. These results show that Stay animals have heightened cytokine gene expression, and both Stay and Escape mice exhibit plasma and neural concentrations of the inflammatory cytokine tumor necrosis factor-α (TNFα) compared to unstressed control mice. Additionally, these results suggest that a single administration of (R)-DOI to Stay animals in low doses, can increase stress coping strategies such as increasing attention to the escape route, promoting escape behavior, and reducing freezing during socially aggressive interaction in the SAM. Lower single doses of (R)-DOI, in addition to shifting behavior to suggest anxiolytic effects, also concomitantly reduce plasma and limbic brain levels of the inflammatory cytokine TNFα.


Subject(s)
Adaptation, Psychological , Aggression , Amphetamines , Hallucinogens , Stress, Psychological , Animals , Male , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Hallucinogens/administration & dosage , Hallucinogens/pharmacology , Adaptation, Psychological/drug effects , Adaptation, Psychological/physiology , Mice , Aggression/drug effects , Aggression/physiology , Amphetamines/pharmacology , Amphetamines/administration & dosage , Mice, Inbred C57BL , Tumor Necrosis Factor-alpha/metabolism , Serotonin 5-HT2 Receptor Agonists/pharmacology , Serotonin 5-HT2 Receptor Agonists/administration & dosage , Escape Reaction/drug effects , Coping Skills
6.
Behav Brain Res ; 467: 115023, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38688411

ABSTRACT

Chronic social stress can increase susceptibility to chronic diseases such as depression. One of the most used models to study the physiological mechanisms and behavioral outcomes of this type of stress is chronic defeat stress (CDS) in male mice. OF1 male mice were subjected to a stress period lasting 18 days. During that time, non-stressed animals were housed in groups. The cluster analysis of the behavioral profile displayed during the first social interaction divided subjects into two groups: active/aggressive (AA) and passive/reactive (PR). The day after the end of the stress period, the following behavioral analyses were performed: the sucrose preference test (SPT) on day 19, the open field test (OFT) on day 20, and the forced swim test (FST) on day 21. Immediately after completing the last test, animals were weighed, and blood samples were obtained. Then, they were sacrificed, and their prefrontal cortices and hippocampi were removed and stored to analyze monoamine levels. Stressed animals displayed anhedonia, and solely the PR mice continued to show higher levels of immobility in the OFT and FST. All stressed animals, regardless of the coping strategy, presented higher plasma corticosterone levels. In addition, stressed mice showed lower levels of tyrosine, dopamine, DOPAC, MHPG, kynurenine, kynurenic acid, and 5-HIAA levels but higher serotonin levels in the prefrontal cortex, not in the hippocampus. In conclusion, our results show that CSD induces differences in monoamine levels between brain areas, and these differences did not respond to the coping strategy adopted.


Subject(s)
Biogenic Monoamines , Corticosterone , Hippocampus , Prefrontal Cortex , Stress, Psychological , Animals , Male , Prefrontal Cortex/metabolism , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Hippocampus/metabolism , Mice , Biogenic Monoamines/metabolism , Corticosterone/blood , Social Defeat , Anhedonia/physiology , Aggression/physiology , Disease Models, Animal
7.
Poult Sci ; 103(5): 103588, 2024 May.
Article in English | MEDLINE | ID: mdl-38479100

ABSTRACT

Preening cups are a form of environmental enrichment that provides Pekin ducks a semi-open water source to express their natural behaviors. We recently observed that preening cups may increase feather pecking behaviors in ducks. Thus, we set out to determine if this form of enrichment can impact the affective state of Pekin ducks. To accomplish this goal, we evaluated the effect of preening cups on serotonin (5-HT) and dopamine (DA) turnover via mass spectrometry and their respective synthetic enzyme gene expression via qRT-PCR. Our study investigated the link between aggressive pecking with levels and activity of brain 5-HT and DA. Brain 5-HT and DA levels and activity have been established for decades to be associated with affective states. Grow-out Pekin ducks (n = 260) were housed at Purdue and raised per industry standards. On day 18, brains were collected from ducks in pens before preening cups were placed (PRE, n = 6) and, again on day 43, in pens with (PC, n = 6) and without (CON, n = 6) preening cups. Brains were dissected into right and left halves, then further microdissected into 4 brain areas: caudal mesencephalon (CM), rostral mesencephalon (RM), diencephalon (DI), and forebrain (FB). The right hemisphere was used for mass spectrometry to determine the neurotransmitter concentration (ng/mg of tissue) and those concentrations were applied to neurotransmitter turnover equations. There were no differences across treatments for 5-HT turnover in any brain area. There were differences in DA turnover across age (P = 0.0067) in the CM and across treatments (P = 0.003) in the RM. The left hemisphere of the brain was used to perform qRT-PCR on the genes of 5-HT and DA production enzymes. Within the CM, day 43 duck brains had increased (P = 0.022) tryptophan hydroxylase and tyrosine hydroxylase relative mRNA levels. All other brain areas showed no differences. Our data suggest that ducks housed with preening cups and that showed increased feather pecking are associated with increased brain DA activity. The increased DA in the brain may lead to a predisposition for increased aggression in the form of feather pecking.


Subject(s)
Brain , Dopamine , Ducks , Housing, Animal , Serotonin , Animals , Ducks/physiology , Dopamine/metabolism , Serotonin/metabolism , Brain/metabolism , Brain/physiology , Behavior, Animal/physiology , Aggression/physiology , Male , Animal Husbandry/methods , Feathers/chemistry
8.
Behav Processes ; 216: 105013, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38460912

ABSTRACT

Social hierarchy is a crucial element for survival, reproduction, fitness, and the maintenance of a stable social group in social animals. This study aimed to investigate the physiological indicators, nociception, unfamiliar female mice preference, spatial learning memory, and contextual fear memory of male mice with different social status in the same cage. Our findings revealed significant differences in the trunk temperature and contextual fear memory between winner and loser mice. However, there were no major discrepancies in body weight, random and fasting blood glucose levels, whisker number, frontal and perianal temperature, spleen size, mechanical and thermal pain thresholds, preference for unfamiliar female mice, and spatial memory. In conclusion, social status can affect mice in multiple ways, and, therefore, its influence should be considered when conducting studies using these animals.


Subject(s)
Aggression , Behavior, Animal , Mice , Male , Female , Animals , Aggression/physiology , Behavior, Animal/physiology , Learning , Social Dominance , Cognition
9.
Nature ; 628(8007): 381-390, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38480888

ABSTRACT

Our understanding of the neurobiology of primate behaviour largely derives from artificial tasks in highly controlled laboratory settings, overlooking most natural behaviours that primate brains evolved to produce1-3. How primates navigate the multidimensional social relationships that structure daily life4 and shape survival and reproductive success5 remains largely unclear at the single-neuron level. Here we combine ethological analysis, computer vision and wireless recording technologies to identify neural signatures of natural behaviour in unrestrained, socially interacting pairs of rhesus macaques. Single-neuron and population activity in the prefrontal and temporal cortex robustly encoded 24 species-typical behaviours, as well as social context. Male-female partners demonstrated near-perfect reciprocity in grooming, a key behavioural mechanism supporting friendships and alliances6, and neural activity maintained a running account of these social investments. Confronted with an aggressive intruder, behavioural and neural population responses reflected empathy and were buffered by the presence of a partner. Our findings reveal a highly distributed neurophysiological ledger of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own.


Subject(s)
Brain , Macaca mulatta , Neurons , Social Behavior , Animals , Female , Male , Aggression/physiology , Brain/cytology , Brain/physiology , Empathy , Grooming , Group Processes , Macaca mulatta/classification , Macaca mulatta/physiology , Macaca mulatta/psychology , Prefrontal Cortex/cytology , Prefrontal Cortex/physiology , Temporal Lobe/cytology , Temporal Lobe/physiology , Neurons/physiology
10.
PLoS One ; 19(2): e0297358, 2024.
Article in English | MEDLINE | ID: mdl-38324564

ABSTRACT

Home cage aggression in group-housed male mice is a major welfare concern and may compromise animal research. Conventional cages prevent flight or retreat from sight, increasing the risk that agonistic encounters will result in injury. Moreover, depending on social rank, mice vary in their phenotype, and these effects seem highly variable and dependent on the social context. Interventions that reduce aggression, therefore, may reduce not only injuries and stress, but also variability between cage mates. Here we housed male mice (Balb/c and SWISS, group sizes of three and five) with or without partial cage dividers for two months. Mice were inspected for wounding weekly and home cages were recorded during housing and after 6h isolation housing, to assess aggression and assign individual social ranks. Fecal boli and fur were collected to quantify steroid levels. We found no evidence that the provision of cage dividers improves the welfare of group housed male mice; The prevalence of injuries and steroid levels was similar between the two housing conditions and aggression was reduced only in Balb/c strain. However, mice housed with cage dividers developed less despotic hierarchies and had more stable social ranks. We also found a relationship between hormone levels and social rank depending on housing type. Therefore, addition of cage dividers may play a role in stabilizing social ranks and modulating the activation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes, thus reducing phenotypic variability between mice of different ranks.


Subject(s)
Aggression , Behavior, Animal , Animals , Male , Mice , Aggression/physiology , Behavior, Animal/physiology , Housing, Animal , Steroids , Hormones
11.
Neuroscience ; 541: 118-132, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38301739

ABSTRACT

Aggression is a social behavior that is critical for survival and reproduction. In adults, circulating gonadal hormones, such as androgens, act on neural circuits to modulate aggressive interactions, especially in reproductive contexts. In many species, individuals also demonstrate aggression before reaching gonadal maturation. Adult male song sparrows, Melospiza melodia, breed seasonally but maintain territories year-round. Juvenile (hatch-year) males aggressively compete for territory ownership during their first winter when circulating testosterone is low. Here, we characterized the relationship between the steroid milieu and aggressive behavior in free-living juvenile male song sparrows in winter. We investigated the effect of a 10 min simulated territorial intrusion (STI) on behavior and steroid levels in blood, 10 microdissected brain regions, and four peripheral tissues (liver, pectoral muscle, adrenal glands, and testes). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we quantified 12 steroids: pregnenolone, progesterone, corticosterone, 11-dehydrocorticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17ß-estradiol, 17α-estradiol, estrone, and estriol. We found that juvenile males are robustly aggressive, like adult males. An STI increases progesterone and corticosterone levels in blood and brain and increases 11-dehydrocorticosterone levels in blood only. Pregnenolone, androgens, and estrogens are generally non-detectable and are not affected by an STI. In peripheral tissues, steroid concentrations are very high in the adrenals. These data suggest that adrenal steroids, such as progesterone and corticosterone, might promote juvenile aggression and that juvenile and adult songbirds might rely on distinct neuroendocrine mechanisms to support similar aggressive behaviors.


Subject(s)
Songbirds , Humans , Animals , Male , Songbirds/physiology , Corticosterone , Progesterone/pharmacology , Chromatography, Liquid , Tandem Mass Spectrometry , Testosterone , Androgens , Aggression/physiology , Estradiol/pharmacology , Pregnenolone/pharmacology
12.
Bioessays ; 46(4): e2300213, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38314963

ABSTRACT

Aggressive behavior is instinctively driven behavior that helps animals to survive and reproduce and is closely related to multiple behavioral and physiological processes. The dorsal raphe nucleus (DRN) is an evolutionarily conserved midbrain structure that regulates aggressive behavior by integrating diverse brain inputs. The DRN consists predominantly of serotonergic (5-HT:5-hydroxytryptamine) neurons and decreased 5-HT activity was classically thought to increase aggression. However, recent studies challenge this 5-HT deficiency model, revealing a more complex role for the DRN 5-HT system in aggression. Furthermore, emerging evidence has shown that non-5-HT populations in the DRN and specific neural circuits contribute to the escalation of aggressive behavior. This review argues that the DRN serves as a multifaceted modulator of aggression, acting not only via 5-HT but also via other neurotransmitters and neural pathways, as well as different subsets of 5-HT neurons. In addition, we discuss the contribution of DRN neurons in the behavioral and physiological aspects implicated in aggressive behavior, such as arousal, reward, and impulsivity, to further our understanding of DRN-mediated aggression modulation.


Subject(s)
Aggression , Dorsal Raphe Nucleus , Animals , Dorsal Raphe Nucleus/metabolism , Aggression/physiology , Serotonin/metabolism , Neurons/metabolism
13.
Nat Neurosci ; 27(4): 702-715, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38347201

ABSTRACT

Social behaviors often consist of a motivational phase followed by action. Here we show that neurons in the ventromedial hypothalamus ventrolateral area (VMHvl) of mice encode the temporal sequence of aggressive motivation to action. The VMHvl receives local inhibitory input (VMHvl shell) and long-range input from the medial preoptic area (MPO) with functional coupling to neurons with specific temporal profiles. Encoding models reveal that during aggression, VMHvl shellvgat+ activity peaks at the start of an attack, whereas activity from the MPO-VMHvlvgat+ input peaks at specific interaction endpoints. Activation of the MPO-VMHvlvgat+ input promotes and prolongs a low motivation state, whereas activation of VMHvl shellvgat+ results in action-related deficits, acutely terminating attack. Moreover, stimulation of MPO-VMHvlvgat+ input is positively valenced and anxiolytic. Together, these data demonstrate how distinct inhibitory inputs to the hypothalamus can independently gate the motivational and action phases of aggression through a single locus of control.


Subject(s)
Aggression , Motivation , Mice , Animals , Aggression/physiology , Social Behavior , Hypothalamus/physiology , Neurons/physiology
14.
Sci Rep ; 14(1): 2957, 2024 02 05.
Article in English | MEDLINE | ID: mdl-38316883

ABSTRACT

Emotional outbursts are displays of intense, challenging behaviour and are prevalent in individuals with neurodevelopmental disorders. Outbursts present a danger to individuals and their carers and are cited as reasons for referral to mental health services. However, it is currently unclear how the characteristics of outbursts may determine their severity. Carers (n = 214) of individuals aged between 6 and 25 and experiencing outbursts at least once per month completed the Emotional Outburst Questionnaire. Questionnaire items were used to compare behaviours observed in most severe and least severe outbursts through quantitative and content analyses of open ended data. Signs of physiological arousal and aggression were seen significantly more in most severe outbursts compared to least severe outbursts. Least severe outbursts were seen more frequently, but most severe outbursts were reported to have a longer duration, be at a higher intensity, and have a longer recovery time. Additionally, associations were found between reduced eye contact and most severe outbursts, as well as expression of suicidal ideation and most severe outbursts. Certain behaviours, notably forms of aggression and physiological arousal, are associated with most severe outbursts. Findings of this study may allow future work examining cross-disorder differences in outbursts to inform targeted interventions aiming to reduce outburst severity and impact. Additionally, identification of such outburst characteristics could aid in measurement of outburst severity, which would allow for more reliable and valid studies on outburst interventions.


Subject(s)
Aggression , Neurodevelopmental Disorders , Humans , Adolescent , Child , Young Adult , Adult , Aggression/physiology , Mood Disorders , Surveys and Questionnaires , Suicidal Ideation
15.
Genes Brain Behav ; 23(1): e12887, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38373143

ABSTRACT

Domesticated animals have been developed by selecting desirable traits following the initial unconscious selection stage, and now exhibit phenotypes desired by humans. Tameness is a common behavioural trait found in all domesticated animals. At the same time, these domesticated animals exhibit a variety of morphological, behavioural, and physiological traits that differ from their wild counterparts of their ancestral species. These traits are collectively referred to as domestication syndrome. However, whether this phenomenon exists is debatable. Previously, selective breeding has been used to enhance active tameness, a motivation to interact with humans, in wild heterogeneous stock mice derived from eight wild inbred strains. In the current study, we used tame mice to study how selective breeding for active tameness affects behavioural and morphological traits. A series of behavioural and morphological analyses on mice showed an increased preference for social stimuli and a longer duration of engagement in non-aggressive behaviour. However, no differences were observed in exploratory or anxiety-related behaviours. Similarly, selection for tameness did not affect ultrasonic vocalisations in mice, and no changes were observed in known morphological traits associated with domestication syndrome. These results suggest that there may be a link between active tameness and sociability and provide insights into the relationship between tameness and other behaviours in the context of domestication.


Subject(s)
Behavior, Animal , Domestication , Humans , Animals , Mice , Behavior, Animal/physiology , Animals, Domestic/genetics , Selective Breeding , Aggression/physiology
16.
Sci Rep ; 14(1): 4087, 2024 02 19.
Article in English | MEDLINE | ID: mdl-38374428

ABSTRACT

Youths with high levels of callous-unemotional (CU) traits and aggression are at an increased risk for developing antisocial behaviours into adulthood. In this population, neurostructural grey matter abnormalities have been observed in the prefrontal cortex. However, the directionality of these associations is inconsistent, prompting some to suggest they may vary across development. Although similar neurodevelopmental patterns have been observed for other disorders featuring emotional and behavioural dysregulation, few studies have tested this hypothesis for CU traits, and particularly not for aggression subtypes. The current study sought to examine grey matter correlates of CU traits and aggression (including its subtypes), and then determine whether these associations varied by age. Fifty-four youths (10-19 years old) who were characterized for CU traits and aggression underwent MRI. Grey matter volume and surface area within the anterior cingulate cortex was positively associated with CU traits. The correlation between CU traits and medial orbitofrontal cortex (mOFC) volume varied significantly as a function of age, as did the correlation between reactive aggression and mOFC surface area. These associations became more positive with age. There were no significant findings for proactive/total aggression. Results are interpreted considering the potential for delayed cortical maturation in youths with high CU traits/aggression.


Subject(s)
Conduct Disorder , Adolescent , Humans , Child , Young Adult , Adult , Aggression/physiology , Emotions/physiology , Antisocial Personality Disorder/diagnostic imaging , Antisocial Personality Disorder/psychology , Prefrontal Cortex/diagnostic imaging
17.
Horm Behav ; 160: 105487, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38281444

ABSTRACT

Oxytocin is a versatile neuropeptide that modulates many different forms of social behavior. Recent hypotheses pose that oxytocin enhances the salience of rewarding and aversive social experiences, and the field has been working to identify mechanisms that allow oxytocin to have diverse effects on behavior. Here we review studies conducted on the California mouse (Peromyscus californicus) that shed light on how oxytocin modulates social behavior following stressful experiences. In this species, both males and females exhibit high levels of aggression, which has facilitated the study of how social stress impacts both sexes. We review findings of short- and long-term effects of social stress on the reactivity of oxytocin neurons. We also consider the results of pharmacological studies which show that oxytocin receptors in the bed nucleus of the stria terminalis and nucleus accumbens have distinct but overlapping effects on social approach behaviors. These findings help explain how social stress can have different behavioral effects in males and females, and how oxytocin can have such divergent effects on behavior. Finally, we consider how new technological developments and innovative research programs take advantage of the unique social organization of California mice to address questions that can be difficult to study in conventional rodent model species. These new methods and questions have opened new avenues for studying the neurobiology of social behavior.


Subject(s)
Oxytocin , Peromyscus , Male , Female , Animals , Oxytocin/pharmacology , Oxytocin/physiology , Peromyscus/physiology , Social Behavior , Aggression/physiology , Receptors, Oxytocin , Rodentia
18.
Nature ; 626(7998): 347-356, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38267576

ABSTRACT

To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.


Subject(s)
Aggression , Avoidance Learning , Hypothalamus , Neural Pathways , Neurons , Oxytocin , Social Learning , Animals , Mice , Aggression/physiology , Avoidance Learning/physiology , Cues , Fear/physiology , Hypothalamus/cytology , Hypothalamus/metabolism , Neural Pathways/physiology , Neurons/metabolism , Oxytocin/metabolism , Receptors, Oxytocin/metabolism , Social Behavior , Social Learning/physiology , Supraoptic Nucleus/cytology , Supraoptic Nucleus/metabolism , Ventromedial Hypothalamic Nucleus/cytology , Ventromedial Hypothalamic Nucleus/metabolism , Neuronal Plasticity
19.
Horm Behav ; 157: 105452, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37977023

ABSTRACT

Social hierarchies are a prevalent feature of all animal groups, and an individual's rank within the group can significantly affect their overall health, typically at the greatest expense of the lowest-ranked individuals, or omegas. These subjects have been shown to exhibit various stress-related phenotypes, such as increased hypothalamic-pituitary axis activity and increased amygdalar corticotropin-releasing factor levels compared to higher-ranked subjects. However, these findings have been primarily characterized in males and in models requiring exhibition of severe aggression. The goals of the current study, therefore, were to characterize the formation and maintenance of social hierarchies using the tube test and palatable liquid competition in same-sex groups of male and female C57BL/6 J mice. We also aimed to examine the effects of tube test-determined social rank on plasma and hypothalamic oxytocin and vasopressin levels, peptides with established roles in social behaviors and the stress response. Lastly, we assessed the effects of environmental enrichment and length of testing on the measures outlined above. Overall, we demonstrated that males and females develop social hierarchies and that these hierarchies can be determined using the tube test. While we were unable to establish a consistent connection between peptide levels and social rank, we observed transient changes in these peptides reflecting complex interactions between social rank, sex, environment, and length of testing. We also found that many male and female omegas began to exhibit passive coping behavior after repeated tube test losses, demonstrating the potential of this assay to serve as a model of chronic, mild psychosocial stress.


Subject(s)
Hierarchy, Social , Social Behavior , Humans , Animals , Mice , Male , Female , Mice, Inbred C57BL , Aggression/physiology , Hypothalamus
20.
Mol Cell Endocrinol ; 580: 112101, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37923055

ABSTRACT

Terrestrial vertebrates have a population of androgen-dependent vasotocin (VT)-expressing neurons in the extended amygdala that are more abundant in males and mediate male-typical social behaviors, including aggression. Teleosts lack these neurons but instead have novel male-specific VT-expressing neurons in the tuberal hypothalamus. Here we found in medaka that vt expression in these neurons is dependent on post-pubertal gonadal androgens and that androgens can act on these neurons to directly stimulate vt transcription via the androgen receptor subtype Ara. Furthermore, administration of exogenous VT induced aggression in females and alterations in the androgen milieu led to correlated changes in the levels of tuberal hypothalamic vt expression and aggression in both sexes. However, genetic ablation of vt failed to prevent androgen-induced aggression in females. Collectively, our results demonstrate a marked androgen dependence of male-specific vt expression in the teleost tuberal hypothalamus, although its relevance to male-typical aggression needs to be further validated.


Subject(s)
Aggression , Oryzias , Animals , Female , Male , Aggression/physiology , Androgens/pharmacology , Androgens/metabolism , Sexual Behavior, Animal/physiology , Vasotocin/metabolism , Oryzias/metabolism , Hypothalamus/metabolism
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