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Kareklas, Kyriacos

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  • Evolutionarily conserved role of oxytocin in social fear contagion in zebrafish
    Publication . Akinrinade, Ibukun; Kareklas, Kyriacos; Teles, Magda C; Reis, Thais K.; Gliksberg, Michael; Petri, Giovanni; Levkowitz, Gil; Oliveira, Rui F.
    Emotional contagion is the most ancestral form of empathy. We tested to what extent the proximate mechanisms of emotional contagion are evolutionarily conserved by assessing the role of oxytocin, known to regulate empathic behaviors in mammals, in social fear contagion in zebrafish. Using oxytocin and oxytocin receptor mutants, we show that oxytocin is both necessary and sufficient for observer zebrafish to imitate the distressed behavior of conspecific demonstrators. The brain regions associated with emotional contagion in zebrafish are homologous to those involved in the same process in rodents (e.g., striatum, lateral septum), receiving direct projections from oxytocinergic neurons located in the pre-optic area. Together, our results support an evolutionary conserved role for oxytocin as a key regulator of basic empathic behaviors across vertebrates. Copyright © 2023 The Authors, some rights reserved.
  • Social zebrafish: Danio rerio as an emerging model in social neuroendocrinology
    Publication . Kareklas, Kyriacos; Teles, Magda C; Nunes, Ana Rita; F. Oliveira, Rui
    The fitness benefits of social life depend on the ability of animals to affiliate with others and form groups, on dominance hierarchies within groups that determine resource distribution, and on cognitive capacities for recognition, learning and information transfer. The evolution of these phenotypes is coupled with that of neuroendocrine mechanisms, but the causal link between the two remains underexplored. Growing evidence from our research group and others demonstrates that the tools available in zebrafish, Danio rerio, can markedly facilitate progress in this field. Here, we review this evidence and provide a synthesis of the state-of-the-art in this model system. We discuss the involvement of generalized motivation and cognitive components, neuroplasticity and functional connectivity across social decision-making brain areas, and how these are modulated chiefly by the oxytocin-vasopressin neuroendocrine system, but also by reward-pathway monoamine signaling and the effects of sex-hormones and stress physiology.
  • Autism-associated gene shank3 is necessary for social contagion in zebrafish
    Publication . Kareklas, Kyriacos; Teles, Magda C; Dreosti, Elena; Oliveira, Rui F.
    Background Animal models enable targeting autism-associated genes, such as the shank3 gene, to assess their impact on behavioural phenotypes. However, this is often limited to simple behaviours relevant for social interaction. Social contagion is a complex phenotype forming the basis of human empathic behaviour and involves attention to the behaviour of others for recognizing and sharing their emotional or affective state. Thus, it is a form of social communication, which constitutes the most common developmental impairment across autism spectrum disorders (ASD). Methods Here we describe the development of a zebrafish model that identifies the neurocognitive mechanisms by which shank3 mutation drives deficits in social contagion. We used a CRISPR-Cas9 technique to generate mutations to the shank3a gene, a zebrafish paralogue found to present greater orthology and functional conservation relative to the human gene. Mutants were first compared to wild types during a two-phase protocol that involves the observation of two conflicting states, distress and neutral, and the later recall and discrimination of others when no longer presenting such differences. Then, the whole-brain expression of different neuroplasticity markers was compared between genotypes and their contribution to cluster-specific phenotypic variation was assessed. Results The shank3 mutation markedly reduced social contagion via deficits in attention contributing to difficulties in recognising affective states. Also, the mutation changed the expression of neuronal plasticity genes. However, only downregulated neuroligins clustered with shank3a expression under a combined synaptogenesis component that contributed specifically to variation in attention. Limitations While zebrafish are extremely useful in identifying the role of shank3 mutations to composite social behaviour, they are unlikely to represent the full complexity of socio-cognitive and communication deficits presented by human ASD pathology. Moreover, zebrafish cannot represent the scaling up of these deficits to higher-order empathic and prosocial phenotypes seen in humans. Conclusions We demonstrate a causal link between the zebrafish orthologue of an ASD-associated gene and the attentional control of affect recognition and consequent social contagion. This models autistic affect-communication pathology in zebrafish and reveals a genetic attention-deficit mechanism, addressing the ongoing debate for such mechanisms accounting for emotion recognition difficulties in autistic individuals.
  • Phenotypic architecture of sociality and its associated genetic polymorphisms in zebrafish
    Publication . Gonçalves, Claúdia; Kareklas, Kyriacos; Teles, Magda C; Varela, Susana.A.M.; Costa, João; Leite, Ricardo B.; Paixão, Tiago; Oliveira, Rui Filipe
    Sociality relies on motivational and cognitive components that may have evolved independently, or may have been linked by phenotypic correlations driven by a shared selective pressure for increased social competence. Furthermore, these components may be domain-specific or of general-domain across social and non-social contexts. Here, we used zebrafish to test if the motivational and cognitive components of social behavior are phenotypically linked and if they are domain specific or of general domain. The behavioral phenotyping of zebrafish in social and equivalent non-social tests shows that the motivational (preference) and cognitive (memory) components of sociality: (1) are independent from each other, hence not supporting the occurrence of a sociality syndrome; and (2) are phenotypically linked to non-social traits, forming two general behavioral modules, suggesting that sociality traits have been co-opted from general-domain motivational and cognitive traits. Moreover, the study of the association between single nucleotide polymorphisms (SNPs) and each behavioral module further supports this view, since several SNPs from a list of candidate “social” genes, are statistically associated with the motivational, but not with the cognitive, behavioral module. Together, these results support the occurrence of general-domain motivational and cognitive behavioral modules in zebrafish, which have been co-opted for the social domain. © 2022 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.