Body patterning and cognition in cephalopods - a literature review

Cephalopods are a valuable model for studying the evolution of cognition due to their distinctive brain structure, organisation, and connectivity patterns compared to vertebrates. The development of large brains and behavioural complexities are believed to be triggered by evolutionary pressures stemming from factors like heightened predation, more demanding foraging conditions, and intense mating competition. While the differences between corvid and mammals are less pronounced, the cephalopod brain is closer to the vertebrate brain in terms of encephalisation of ganglionic masses observed by nerve cell clusters. The cerebral ganglion in cephalopods is similar to the vertebrate forebrain and midbrain, while the vertical lobe is similar to the vertebrate cerebral cortex and hippocampus formation, which are involved in learning and memory. These brain regions function in a hierarchical system and are intimately connected with their eyes and optic lobes where visual inputs are processed, motor commands are transmitted to the lower motor centre. Chromatophores are skin elements and the physiological control of body patterning and are visually driven and light sensitive. This sets cephalopods apart from their molluscan families such as gastropods and bivalves. Recent studies have revealed that the opsins present in the skin are like those occurring in the retina. This infers that the connection between visual processing and body patterns is not exclusively innate. Expanding on Macphail's Null Hypothesis which posits no significant qualitative or quantitative differences in intelligence across vertebrates, this study seeks to explore the link between body patterning and cognitive abilities across cephalopod species. By comparing patterns of similarities and differences in cognitive abilities, this study aims to investigate whether body patterning can serve as an indicator of cognitive capacity. In conclusion, the study finds the presence of interindividual variations within species and disparities across different species in both body patterning and cognitive abilities. There are associations between cognitive capacity and body patterns. However, establishing a direct and conclusive connection between high-level cognitive abilities and the expression of body patterns remains elusive, as concrete evidence supporting such a relationship is lacking.Cephalopoda utgör en värdefull modell för att studera den kognitiva evolutionen på grund av deras distinkta hjärnstruktur, organisation och nervernas kontaktmönster jämfört med ryggradsdjur. Utvecklingen av stora hjärnor och komplexa beteenden tros vara resultatet av evolutionär press från faktorer som ökad predation, mer krävande födosökningsförhållanden och intensiv parningskonkurrens. Medan skillnaderna mellan kråkfåglar och däggdjur är mindre uttalade, är bläckfiskhjärnan närmare ryggradsdjurshjärnan när det gäller encefalisering av nervcellkluster. Det cerebrala ganglie hos bläckfiskar liknar ryggradsdjurens främre hjärna och mellanhjärna, medan den vertikala loben liknar ryggradsdjurens hjärnbark och hippocampusformation, som är involverade i inlärning och minne. Dessa hjärnregioner fungerar inom ett hierarkiskt system och är intimt kopplade till deras ögon och optiska lober där visuell information bearbetas och motoriska kommandon överförs till de nedre motoriska centrarna. Kromatoforer är hudstrukturer som fysiologiskt kontrollerar kroppsmönster och är visuellt styrda och ljuskänsliga. Detta skiljer cephalopoder från andra molluskfamiljer som gastropoder och musslor. Studier har nyligenavslöjat att de opsin som finns i huden liknar de som förekommer i näthinnan. Detta antyder att sambandet mellan visuell bearbetning och kroppsmönster inte är uteslutande medfödd. Utöver Macphails nollhypotes, som hävdar att det inte finns några signifikanta kvalitativa eller kvantitativa skillnader i intelligens mellan ryggradsdjur, ämnar denna studie utforska kopplingen mellan kroppsmönster och kognitiva förmågor hos cephalopoda. Genom att jämföra likheter och skillnader i kognitiva förmågor syftar denna studie till att undersöka om kroppsmönster kan fungera som en indikator på kognitiv kapacitet. Resultaten visar på förekomst av variationer mellan individer inom arter och skillnader mellan olika arter både vad gäller kroppsmönster och kognitiva förmågor. Det finns samband mellan kognitiv kapacitet och funktioner samt kroppsmönster. Dock är det fortfarande svårt att fastställa en direkt och definitiv koppling mellan hög kognitiva förmågor och uttrycket av kroppsmönster, eftersom konkret bevis som stöder ett sådant samband saknas

Social Preference in Juvenile Zebrafish

Social behaviours are essential for the survival and reproduction of many species, including our own. A fundamental feature of all social behaviour is social preference, which is an individual’s propensity to interact with members of their species (termed conspecifics). In an average population, various social preference behaviours are readily observed, ranging from uninterested (not engaging with conspecifics) to very social (engaging with conspecifics). Individuals expressing these behaviours are typically labelled as having an asocial or prosocial, respectively. Little is known about how the underlying social circuitry gives rise to such distinct social behaviours in the population. It is well established that adverse social experiences can impact social behaviour, including isolation during early development. Undesired social isolation (loneliness) alters behavioural patterns, neuroanatomy (e.g., brain volume) and neurochemistry in ways that resemble developmental neuropsychiatric disorders, including autism and schizophrenia. However, few studies have investigated the impact of early life isolation on social circuitry, and how this results in dysfunctional social behaviour commonly associated with these and other disorders. In this thesis, juvenile zebrafish was used to model social preference behaviour, as it is an excellent translational model for human developmental and behavioural disorders. Population-level analysis revealed that several features of social preference behaviour could be summarised via Visual Preference Index (VPI) scores representing sociality. Using multiple behavioural parameters, comprehensive investigations of asocial and prosocial fish identified via VPIs revealed distinct responses towards conspecifics between the two phenotypes. These initial results served as a baseline for facilitating the identification of atypical social behaviour following periods of social isolation. The impact of isolation on social preference was assessed by applying either the full isolation over the initial three weeks of development or partial isolation, 48 hours or 24 hours, before testing. Following periods of social isolation, juvenile zebrafish displayed anxiety-like behaviours. Furthermore, full and partial isolation of 48 hours, but not 24 hours, altered responses to conspecifics. To assess the impact of social isolation on the social circuitry, the brain activities of fish were analysed and compared between different rearing conditions using high-resolution two-photon imaging. Whole-brain functional maps of isolated social phenotypes were distinct from those in the average population. Isolation-induced activity changes were found mainly in brain regions linked to social behaviour, social cue processing, and anxiety/stress (e.g., the caudal hypothalamus and preoptic area). Since some of these affected regions are modulated by serotonin, the reversibility of the adverse effects of social isolation on preference behaviour was investigated by using pharmacological manipulation of the monoaminergic system. The administration of an anxiolytic the drug buspirone demonstrated that altered social preference behaviour in isolated fish could be rescued by acutely reducing serotonin levels. By investigating social preference at the behavioural and functional level in wild-type juvenile zebrafish, this work contributes to our understanding of how the social brain circuity produces diverse social preferences. Furthermore, it provides important information on how early-life environmental adversity gives rise to atypical social behaviour and the neurotransmitters modulating the circuit, offering new opportunities for effective intervention

Not just for fun! social play as a springboard for adult social competence in human and non-human primates

Play is one of the most difficult behaviors to quantify and for this reason, its study has had a very rocky history. Social play is ephemeral, difficult to distinguish from the other so-called serious behaviors, not so frequent (especially in sexually mature subjects), fast, and complex to describe. Due to its multifaceted nature, it has often been considered as a wastebasket category that has included all kinds of the behaviors not showing any immediate, obvious goal. Yet, play is widespread across the whole primate order and can have a strong impact on the development of cognitive, psychological, and social skills of many species, including humans. Unlike functional behaviors that are specifically and economically performed to reduce uncertainty and to increase the opportunity to gain resources, play seems to introduce and increase uncertainty, creating new challenges for the animals. For this reason, social play has been hypothesized to be the engine of behavioral innovation in ontogeny. From the first mild and gentle interactions with the mother to the most sophisticated play fighting sessions and acrobatic action sequences with peers, play represents for juveniles (and not only for them!) a window onto the social and physical environment. In this review, I focus on social play and its relation to adult social competence. By playing, juveniles acquire competence to manage interactions with conspecifics, enlarge their social networks, and test their physical power and motor skills (i.e., long-term benefits). At the same time, I propose the view that play—due to its plastic and versatile nature—can be used in an opportunistic way, as a joker behavior, throughout life to strategically obtain short-term or immediate benefits. I put forward the hypothesis that, during ontogeny, the joker function of play can be modulated according to the differing inter-individual relationships present in the diverse societies, characterizing the primate order

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Pleiotropic effects of candidate genes on autism spectrum disorder and comorbidities: genetics, funcional studies and animal models

[eng] Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, as well as repetitive and restricted patterns of behaviour. Although growing evidence supports a main contribution of genetic factors to its neurobiology and hundreds of candidate genes have been identified in recent years, the genetic architecture of the disorder is still not fully understood. Moreover, ASD frequently co-occurs with other developmental and psychiatric disorders, and shared genetic mechanisms are hypothesized to underlie these comorbidities. In this doctoral thesis, we aimed to study the contribution of several candidate genes to ASD and comorbidities. We have focused on the 14-3-3 gene family, RBFOX1 and the BEX/TCEAL gene family, performed genetic and functional studies and further characterized the neurobiological effects of their deficiency using animal models. First, our results suggest a role for the 14-3-3 genes in ASD and schizophrenia (SCZ). Ultra-rare variants in the 14-3-3 genes are enriched in ASD and common and rare variants in the YWHAE and YWHAZ genes, respectively, are associated with SCZ. We have also reported alterations in the expression of these genes in postmortem brains of ASD or SCZ patients. Furthermore, we have demonstrated a loss-of-function effect of a damaging variant in the YWHAZ gene present in two siblings with ASD and attention deficit/hyperactivity disorder (ADHD). In addition, we have characterized ywhaz expression in zebrafish across development and in adulthood and demonstrated that ywhaz depletion causes alterations in behaviour, in neuronal activity and connectivity and in monoamine signalling. The behavioural changes included freezing and were rescued with drug treatments that target monoamine neurotransmission. Second, we have demonstrated a relevant contribution of common variants in RBFOX1 to psychiatric disorders and traits. Also, we have shown that a high number of copy number variants (CNVs) spanning RBFOX1 are reported in patients with psychiatric conditions, the vast majority in patients with ASD or SCZ, and patients with these disorders also show a decreased expression of RBFOX1 in cortex. Finally, we have used knockout animal models to understand its role in psychiatric disorders, and demonstrated that both mice and zebrafish RBFOX1- deficient models present behavioural alterations that can be related to neurodevelopmental disorders such as ASD, ADHD and SCZ. Third, we found that all BEX/TCEAL genes are downregulated in postmortem brain regions of ASD and SCZ patients and that rare CNVs spanning several BEX/TCEAL genes have been reported in patients with severe neurodevelopmental problems. Furthermore, Bex3-deficient mice show anatomical and molecular alterations in brain, an excitatory/inhibitory imbalance and behavioural alterations that can be assimilated to ASD- and SCZ-like symptoms.[spa] El trastorno del espectro autista (TEA) es un trastorno del neurodesarrollo caracterizado por problemas en la comunicación e interacción social, así como patrones restrictivos y repetitivos de comportamiento. El peso de la genética en su etiología es cada vez más evidente, aunque la compleja arquitectura genética del trastorno sigue siendo una incógnita. Además, el diagnóstico de otros trastornos comórbidos es frecuente en pacientes con TEA, por lo que se hipotetiza una base genética común. El objetivo de esta tesis doctoral es elucidar la contribución de varios genes candidatos, concretamente la familia de genes 14-3-3, el gen RBFOX1 y la familia BEX/TCEAL, al TEA y otros trastornos comórbidos, realizando estudios genéticos y funcionales, así como caracterizando los efectos neurobiológicos de su deficiencia en modelos animales. En primer lugar, nuestros resultados sugieren que variantes ultra-raras en los genes 14-3-3 contribuyen al TEA y que variantes comunes y raras en los genes YWHAE y YWHAZ, respectivamente, están asociadas a esquizofrenia (SCZ). Además, la expresión de los genes 14- 3-3 está alterada en pacientes con TEA o SCZ. Hemos demostrado que una variante patogénica en el gen YWHAZ presente en dos hermanos con TEA y trastorno de déficit de atención e hiperactividad (TDAH) provoca una pérdida de función de la proteína. Asimismo, hemos demostrado que la deleción de ywhaz produce alteraciones en la actividad y conectividad neuronal, la señalización monoaminérgica y el comportamiento, pudiéndose este último recuperar mediante fármacos. En segundo lugar, hemos demostrado que variantes comunes en RBFOX1 están asociadas a diferentes trastornos psiquiátricos y que un número elevado de variantes del número de copias (CNV) afectan a RBFOX1 en pacientes con trastornos psiquiátricos, siendo especialmente frecuentes en pacientes con TEA o SCZ que, además, presentan una disminución en la expresión de RBFOX1 en corteza cerebral. Asimismo, hemos usado modelos animales genoanulados para estudiar la implicación de RBFOX1 en trastornos psiquiátricos, demostrando que tanto el modelo murino como los de pez cebra presentan alteraciones de comportamiento relacionadas con trastornos del neurodesarrollo, como ASD, TDAH y SCZ. Por último, la expresión de los genes BEX/TCEAL está disminuida en regiones cerebrales de pacientes con TEA o SCZ y, además, se han descrito CNVs que abarcan varios genes BEX/TCEAL en pacientes con trastornos severos del neurodesarrollo. Los ratones genoanulados para Bex3 muestran alteraciones anatómicas y moleculares en cerebro, un desequilibro excitación/inhibición y alteraciones de comportamiento asimilables a síntomas de TEA y SCZ

Applying welfare science to cetacean strandings : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Zoology at Massey University, Albany, New Zealand

Animal welfare science can provide critical knowledge to inform ethical wildlife management and human intervention efforts. Despite live stranding events being recognised by the International Whaling Commission as a major welfare concern for free-ranging cetaceans, little research has to date, been conducted on stranded cetacean welfare. Live cetacean stranding events offer a quintessential exemplar of wildlife management, where assessment or integration of welfare has been limited in the decision-making process. This thesis contributes new understanding of how welfare science can be applied to cetacean stranding events to inform decision-making processes. Here, the first welfare-centric data regarding live stranded cetaceans is presented. Specifically, this research presents novel contributions to science via: (1) conceptualisation of stranded cetacean welfare and survival likelihood; (2) recognition of key knowledge gaps and concerns that must be addressed to ensure optimal welfare and survival likelihood outcomes; (3) identification of potential valuable and practical indicators for assessing stranded cetacean welfare and survival likelihood; (4) evidenced feasibility of welfare indicator application to live cetacean stranding events; (5) incorporation of indicators to undertake holistic welfare assessments; (6) identification of potential welfare implications of strandings management, including efficacy of euthanasia; and (7) provision of key recommendations and requirements to ensure humane end-of-life outcomes for non-viable stranded cetaceans. This thesis documents inextricable links between animal welfare and survival likelihood of stranded cetaceans and demonstrates a clear need for integration of welfare science alongside conservation biology at live stranding events. Systematic, standardised data collection and welfare-centric assessment of stranded cetaceans can, if applied scientifically, inform intervention decisions, to ensure consistent guidance and improve strandings management to safeguard humane outcomes for affected cetaceans. Collectively, this research provides a significant contribution to the current scientific understanding of stranded cetacean welfare, by providing key knowledge required for the development of a welfare assessment framework that can support decision-making at stranding events