Publications by authors named "Hector Carreño Gutiérrez"

11 Publications

  • Page 1 of 1

Skin swabbing is a refined technique to collect DNA from model fish species.

Sci Rep 2020 10 23;10(1):18212. Epub 2020 Oct 23.

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK.

Model fish species such as sticklebacks and zebrafish are frequently used in studies that require DNA to be collected from live animals. This is typically achieved by fin clipping, a procedure that is simple and reliable to perform but that can harm fish. An alternative procedure to sample DNA involves swabbing the skin to collect mucus and epithelial cells. Although swabbing appears to be less invasive than fin clipping, it still requires fish to be netted, held in air and handled-procedures that can cause stress. In this study we combine behavioural and physiological analyses to investigate changes in gene expression, behaviour and welfare after fin clipping and swabbing. Swabbing led to a smaller change in cortisol release and behaviour on the first day of analysis compared to fin clipping. It also led to less variability in data suggesting that fewer animals need to be measured after using this technique. However, swabbing triggered some longer term changes in zebrafish behaviour suggesting a delayed response to sample collection. Skin swabbing does not require the use of anaesthetics and triggers fewer changes in behaviour and physiology than fin clipping. It is therefore a more refined technique for DNA collection with the potential to improve fish health and welfare.
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http://dx.doi.org/10.1038/s41598-020-75304-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584585PMC
October 2020

The zebrafish histamine H3 receptor modulates aggression, neural activity and forebrain functional connectivity.

Acta Physiol (Oxf) 2020 12 12;230(4):e13543. Epub 2020 Aug 12.

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, UK.

Aim: Aggression is a behavioural trait characterized by the intention to harm others for offensive or defensive purposes. Neurotransmitters such as serotonin and dopamine are important mediators of aggression. However, the physiological role of the histaminergic system during this behaviour is currently unclear. Here, we aimed to better understand histaminergic signalling during aggression by characterizing the involvement of the histamine H3 receptor (Hrh3).

Methods: We have generated a novel zebrafish Hrh3 null mutant line using CRISPR-Cas9 genome engineering and investigated behavioural changes and alterations to neural activity using whole brain Ca imaging in zebrafish larvae and ribosomal protein S6 (rpS6) immunohistochemistry in adults.

Results: We show that genetic inactivation of the histamine H3 receptor (Hrh3) reduces aggression in zebrafish, an effect that can be reproduced by pharmacological inhibition. In addition, hrh3 zebrafish show behavioural impairments consistent with heightened anxiety. Larval in vivo whole brain Ca imaging reveals higher neuronal activity in the forebrain of mutants, but lower activity in specific hindbrain areas and changes in measures of functional connectivity between subregions. Adult hrh3 zebrafish display brain region-specific neural activity changes in response to aggression of both key regions of the social decision-making network, and the areas containing histaminergic neurons in the zebrafish brain.

Conclusion: These results highlight the importance of zebrafish Hrh3 signalling for aggression and anxiety and uncover the brain areas involved. Targeting this receptor might be a potential novel therapeutic route for human conditions characterized by heightened aggression.
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http://dx.doi.org/10.1111/apha.13543DOI Listing
December 2020

Screening for drugs to reduce zebrafish aggression identifies caffeine and sildenafil.

Eur Neuropsychopharmacol 2020 01 1;30:17-29. Epub 2019 Nov 1.

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester LE1 7RH, UK. Electronic address:

Although aggression is a common symptom of psychiatric disorders the drugs available to treat it are non-specific and can have unwanted side effects. In this study we have used a behavioural platform in a phenotypic screen to identify drugs that can reduce zebrafish aggression without affecting locomotion. In a three tier screen of ninety-four drugs we discovered that caffeine and sildenafil can selectively reduce aggression. Caffeine also decreased attention and increased impulsivity in the 5-choice serial reaction time task whereas sildenafil showed the opposite effect. Imaging studies revealed that both caffeine and sildenafil are active in the zebrafish brain, with prominent activation of the thalamus and cerebellum evident. They also interact with 5-HT neurotransmitter signalling. In summary, we have demonstrated that juvenile zebrafish are a suitable model to screen for novel drugs to reduce aggression, with the potential to uncover the neural circuits and signalling pathways that mediate such behavioural effects.
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http://dx.doi.org/10.1016/j.euroneuro.2019.10.005DOI Listing
January 2020

Correction: The three-spined stickleback as a model for behavioural neuroscience.

PLoS One 2019 1;14(5):e0216518. Epub 2019 May 1.

[This corrects the article DOI: 10.1371/journal.pone.0213320.].
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216518PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493743PMC
May 2019

The three-spined stickleback as a model for behavioural neuroscience.

PLoS One 2019 26;14(3):e0213320. Epub 2019 Mar 26.

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, United Kingdom.

The three-spined stickleback (Gasterosteus aculeatus) is a small teleost fish that is ubiquitous across the Northern Hemisphere. Among the behaviours that have been characterised in this species is ritualized courtship, aggressiveness and parental behaviour. Whereas three-spined sticklebacks have been used for ecological, evolutionary, parasitological and toxicological research, its complex behavioural repertoire and experimental advantages have not been exploited for basic neuroscience research. The aim of the present study is to describe some innate behaviours of laboratory bred three-spined sticklebacks by using a battery of tests that have been developed and validated to model some aspects of human psychiatric disorders in zebrafish. We recorded mirror induced aggression, novel object boldness, shoaling, and anxiety-like behaviour using both the novel tank diving and the black-white preference tests. We show that behaviour of three-spined sticklebacks in these standard tests is remarkably similar to that of zebrafish and other species and can be altered by fluoxetine and buspirone. These findings highlight the potential of using three-spined sticklebacks for cross-species and translational studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213320PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435232PMC
December 2019

Endothelin neurotransmitter signalling controls zebrafish social behaviour.

Sci Rep 2019 02 28;9(1):3040. Epub 2019 Feb 28.

Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK.

The formation of social groups is an adaptive behaviour that can provide protection from predators, improve foraging and facilitate social learning. However, the costs of proximity can include competition for resources, aggression and kleptoparasitism meaning that the decision whether to interact represents a trade-off. Here we show that zebrafish harbouring a mutation in endothelin receptor aa (ednraa) form less cohesive shoals than wild-types. ednraa mutants exhibit heightened aggression and decreased whole-body cortisol levels suggesting that they are dominant. These behavioural changes correlate with a reduction of parvocellular arginine vasopressin (AVP)-positive neurons in the preoptic area, an increase in the size of magnocellular AVP neurons and a higher concentration of 5-HT and dopamine in the brain. Manipulation of AVP or 5-HT signalling can rescue the shoaling phenotype of ednraa providing an insight into how the brain controls social interactions.
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http://dx.doi.org/10.1038/s41598-019-39907-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395658PMC
February 2019

MicroRNA degradation by a conserved target RNA regulates animal behavior.

Nat Struct Mol Biol 2018 03 26;25(3):244-251. Epub 2018 Feb 26.

Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.

microRNAs (miRNAs) repress target transcripts through partial complementarity. By contrast, highly complementary miRNA-binding sites within viral and artificially engineered transcripts induce miRNA degradation in vitro and in cell lines. Here, we show that a genome-encoded transcript harboring a near-perfect and deeply conserved miRNA-binding site for miR-29 controls zebrafish and mouse behavior. This transcript originated in basal vertebrates as a long noncoding RNA (lncRNA) and evolved to the protein-coding gene NREP in mammals, where the miR-29-binding site is located within the 3' UTR. We show that the near-perfect miRNA site selectively triggers miR-29b destabilization through 3' trimming and restricts its spatial expression in the cerebellum. Genetic disruption of the miR-29 site within mouse Nrep results in ectopic expression of cerebellar miR-29b and impaired coordination and motor learning. Thus, we demonstrate an endogenous target-RNA-directed miRNA degradation event and its requirement for animal behavior.
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http://dx.doi.org/10.1038/s41594-018-0032-xDOI Listing
March 2018

Automatic quantification of juvenile zebrafish aggression.

J Neurosci Methods 2018 02 21;296:23-31. Epub 2017 Dec 21.

Department of Neuroscience, Psychology and Behaviour, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, LE1 7RH, UK. Electronic address:

Background: Although aggression is a common symptom of psychiatric disorders the drugs available to treat it are non-specific and can have unwanted side effects. The zebrafish is an ideal model for aggression research. Zebrafish are small, amenable to genetic and pharmacological manipulation, and agonistic behaviour can be measured reliably.

New Method: In this study we have established a novel setup to automatically quantify aggression and locomotion in one-month old juvenile zebrafish, a stage at which fish exhibit adult-like behaviour but are small so that one camera can film several animals.

Results: We have validated our novel software by comparison to manual quantification of behaviour, characterised the aggression of one-month old fish, and demonstrated that we can detect alterations to aggression caused by mutation or drug application.

Comparison With Other Methods: The ability to record up to 12 juvenile fish allows us to speed up and standardise data acquisition compared to studies of single fish.

Conclusions: This setup appears to be suitable to screen for drugs that decrease zebrafish aggression as a first step toward developing novel treatments for this behaviour.
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http://dx.doi.org/10.1016/j.jneumeth.2017.12.012DOI Listing
February 2018

Nitric oxide interacts with monoamine oxidase to modulate aggression and anxiety-like behaviour.

Eur Neuropsychopharmacol 2020 01 23;30:30-43. Epub 2017 Sep 23.

Department of Neuroscience, Psychology and Behaviour, University of Leicester, University Rd, Leicester, LE1 7RH, UK. Electronic address:

Nitric oxide (NO) is a gaseous neurotransmitter that has important behavioural functions in the vertebrate brain. In this study we compare the impact of decreased nitric NO signalling upon behaviour and neurobiology using both zebrafish and mouse. nitric oxide synthase mutant (nos1) zebrafish show significantly reduced aggression and an increase in anxiety-like behaviour without altered production of the stress hormone cortisol. Nos1 mice also exhibit decreased aggression and are hyperactive in an open field test. Upon reduction of NO signalling, monoamine neurotransmitter metabolism is reduced as a consequence of decreased Monoamine oxidase activity. Treatment of nos1 zebrafish with the 5-HT receptor 1A agonist 8-OH-DPAT rescues aggression and some aspects of anxiety-like behaviour. Taken together, the interplay between NO and 5-HT appears to be critical to control behaviour. Our cross-species approach challenges the previous notion that reduced neuronal NOS leads to increased aggression. Rather, Nos1 knock-out can also lead to decreased aggression in some situations, a finding that may have implications for future translational research.
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http://dx.doi.org/10.1016/j.euroneuro.2017.09.004DOI Listing
January 2020

Aggression in non-human vertebrates: Genetic mechanisms and molecular pathways.

Am J Med Genet B Neuropsychiatr Genet 2016 07 18;171(5):603-40. Epub 2015 Aug 18.

Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK.

Aggression is an adaptive behavioral trait that is important for the establishment of social hierarchies and competition for mating partners, food, and territories. While a certain level of aggression can be beneficial for the survival of an individual or species, abnormal aggression levels can be detrimental. Abnormal aggression is commonly found in human patients with psychiatric disorders. The predisposition to aggression is influenced by a combination of environmental and genetic factors and a large number of genes have been associated with aggression in both human and animal studies. In this review, we compare and contrast aggression studies in zebrafish and mouse. We present gene ontology and pathway analyses of genes linked to aggression and discuss the molecular pathways that underpin agonistic behavior in these species. © 2015 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajmg.b.32358DOI Listing
July 2016

Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes.

PLoS One 2014 28;9(2):e90393. Epub 2014 Feb 28.

Biomembrane Laboratory, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina ; IMBICE-CONICET, CCT La Plata, Argentina.

Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090393PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938724PMC
October 2014