Fraser J Combe | Manchester Metropolitan University (original) (raw)

Papers by Fraser J Combe

Research paper thumbnail of Genetic drift drives rapid speciation of an Arctic insular endemic shrew ( Sorex pribilofensis )

Research paper thumbnail of Consumer roles of small mammals within fragmented native tallgrass prairie

Research paper thumbnail of Rapid novel microsatellite development using Illumina MiSeq in the critically endangered mountain bongo (Traglephus eurycerus isacci)

Research paper thumbnail of Population genomics of free‐ranging Great Plains white‐tailed and mule deer reflects a long history of inter‐specific hybridization

Evolutionary Applications

Research paper thumbnail of Origins and diversity of the Bering Sea Island fauna: shifting linkages across the northern continents

Biodiversity and Conservation

Research paper thumbnail of The different effects of periodic experimental tree removal patterns on the population demography of the hazel dormice (Muscardinus avellanarius) in a conifer plantation

Research paper thumbnail of {"__content__"=>"Rapid isolation and characterization of microsatellites in the critically endangered mountain bongo ().", "i"=>{"__content__"=>"Tragelaphus eurycerus isaaci"}}

Journal of genetics, 2018

High-throughput sequencing tools promise to revolutionize many aspects of genetic research, e.g. ... more High-throughput sequencing tools promise to revolutionize many aspects of genetic research, e.g. by allowing the identification of functional adaptive genetic variation. However, the expense and expertise required to apply these tools to basic conservation questions is a challenge for applications outside academia, resulting in a so-called 'conservation genomics gap' (Shafer . 2015). The conservation genetics paradigm is that, basic information about inbreeding and gene flow are often critical to inform conservation management of small populations (Ouborg . 2010). This information is often needed quickly and ideally should be accessible to workers without special expertise in genomics (DeSalle and Amato 2004). While the inferential power of highthroughput sequencing to interrogate the genome is profound, the cost for population analysis is higher (though decreasing) than for traditional neutral markers. Thus, the use of neutral markers is still relevant in conservation appli...

Research paper thumbnail of Rapid isolation and characterization of microsatellites from the genome of Asian arowana (Scleropages formosus, Osteoglossidae, Pisces)

Molecular Ecology, 2000

ABSTRACT

Research paper thumbnail of Multi‐individual Microsatellite identification: a multiple genome approach to microsatellite design (MiMi)

Molecular Ecology Resources, Aug 27, 2019

Research paper thumbnail of Using integrated population modelling in conservation monitoring: A case study in the common dormouse (Muscardinus avellanarius)

Research paper thumbnail of After the Ice Age: The Impact of Post-Glacial Dispersal on the Phylogeography of a Small Mammal, Muscardinus avellanarius

Research paper thumbnail of Developmental role of acetylcholinesterase in impulse control in zebrafish

Frontiers in behavioral neuroscience, 2015

Cellular and molecular processes that mediate individual variability in impulsivity, a key behavi... more Cellular and molecular processes that mediate individual variability in impulsivity, a key behavioral component of many neuropsychiatric disorders, are poorly understood. Zebrafish heterozygous for a nonsense mutation in ache (ache (sb55/+)) showed lower levels of impulsivity in a 5-choice serial reaction time task (5-CSRTT) than wild type and ache(+∕+). Assessment of expression of cholinergic (nAChR), serotonergic (5-HT), and dopamine (DR) receptor mRNA in both adult and larval (9 dpf) ache (sb55/+) revealed significant downregulation of chrna2, chrna5, and drd2 mRNA in ache (sb55/+) larvae, but no differences in adults. Acute exposure to cholinergic agonist/antagonists had no effect on impulsivity, supporting the hypothesis that behavioral effects observed in adults were due to lasting impact of developmental alterations in cholinergic and dopaminergic signaling. This shows the cross-species role of cholinergic signaling during brain development in impulsivity, and suggests zebraf...

Research paper thumbnail of The utility of zebrafish to study the mechanisms by which ethanol affects social behavior and anxiety during early brain development

Exposure to moderate levels of ethanol during brain development has a number of effects on social... more Exposure to moderate levels of ethanol during brain development has a number of effects on social behavior but the molecular mechanisms that mediate this are not well understood. Gaining a better understanding of these factors may help to develop therapeutic interventions in the future. Zebrafish offer a potentially useful model in this regard. Here, we introduce a zebrafish model of moderate prenatal ethanol exposure. Embryos were exposed to 20 mM ethanol for seven days (48hpf–9dpf) and tested as adults for individual social behavior and shoaling. We also tested their basal anxiety with the novel tank diving test. We found that the ethanol-exposed fish displayed reductions in social approach and shoaling, and an increase in anxiety in the novel tank test. These behavioral differences corresponded to differences in hrt1aa, slc6a4 and oxtr expression. Namely, acute ethanol caused a spike in oxtr and ht1aa mRNA expression, which was followed by down-regulation at 7dpf, and an up-regulation in slc6a4 at 72hpf. This study confirms the utility of zebrafish as a model system for studying the molecular basis of developmental ethanol exposure. Furthermore, it proposes a putative developmental mechanism characterized by ethanol-induced OT inhibition leading to suppression of 5-HT and up-regulation of 5-HT1A, which leads, in turn, to possible homeostatic up-regulation of 5-HTT at 72hpf and subsequent imbalance of the 5-HT system.

Research paper thumbnail of Development and implementation of a three-choice serial reaction time task for zebrafish ( Danio rerio)

Behavioural Brain Research, 2000

Zebrafish are an established and widely utilized developmental genetic model system, but limitati... more Zebrafish are an established and widely utilized developmental genetic model system, but limitations in developed behavioral assays have meant that their potential as a model in behavioral neuroscience has yet to be fully realized. Here, we describe the development of a novel operant behavioral assay to examine a variety of aspects of stimulus control in zebrafish using a 3 choice

Research paper thumbnail of Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood

Addiction Biology, 2014

Exposure to alcohol during early central nervous system development has been shown variously to a... more Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning.

Research paper thumbnail of Housing conditions differentially affect physiological and behavioural stress responses of zebrafish, as well as the response to anxiolytics

PloS one, 2012

Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advan... more Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advances in our understanding of zebrafish behaviour, their utility as a comparative model in behavioural neuroscience is beginning to be realised. One widely reported behavioural measure is the novel tank-diving assay, which has been often cited as a test of anxiety and stress reactivity. Despite its wide utilisation, and various validations against anxiolytic drugs, reporting of pre-test housing has been sparse in the literature. As zebrafish are a shoaling species, we predicted that housing environment would affect their stress reactivity and, as such, their response in the tank-diving procedure. In our first experiment, we tested various aspects of housing (large groups, large groups with no contact, paired, visual contact only, olfactory contact only) and found that the tank diving response was mediated by visual contact with conspecifics. We also tested the basal cortisol levels of grou...

Research paper thumbnail of The utility of zebrafish to study the mechanisms by which ethanol affects social behavior and anxiety during early brain development

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014

Research paper thumbnail of Discrimination reversal and attentional sets in zebrafish (Danio rerio)

Behavioural Brain Research, 2012

The potential of zebrafish as a comparative model in behavioural neuroscience is currently hamper... more The potential of zebrafish as a comparative model in behavioural neuroscience is currently hampered only by the lack of reliable and validated behavioural assays available to researchers. In the present experiment, we describe the performance of zebrafish in a test of attentional set formation. The fish were initially trained on a two-choice colour discrimination. Upon reaching acquisition criterion, the reinforced alternative was switched to the previously unreinforced alternative. Again, upon reaching criterion, the cues were replaced with a novel pair of colours (intra-dimensional shift) and reversed again on reaching criteria. We found that zebrafish show a steady decrease in trials-to-criteria over the four phases of the experiment, suggesting that they are forming and maintaining an attentional set, as has previously been demonstrated with mammals. Reversal learning deficits have been implicated in a variety of human psychological disorders (e.g., disorders of impulse control) and as such, we propose that performance of zebrafish in this procedure may represent a useful comparative model to complement existing rodent models.

Research paper thumbnail of Genetic drift drives rapid speciation of an Arctic insular endemic shrew ( Sorex pribilofensis )

Research paper thumbnail of Consumer roles of small mammals within fragmented native tallgrass prairie

Research paper thumbnail of Rapid novel microsatellite development using Illumina MiSeq in the critically endangered mountain bongo (Traglephus eurycerus isacci)

Research paper thumbnail of Population genomics of free‐ranging Great Plains white‐tailed and mule deer reflects a long history of inter‐specific hybridization

Evolutionary Applications

Research paper thumbnail of Origins and diversity of the Bering Sea Island fauna: shifting linkages across the northern continents

Biodiversity and Conservation

Research paper thumbnail of The different effects of periodic experimental tree removal patterns on the population demography of the hazel dormice (Muscardinus avellanarius) in a conifer plantation

Research paper thumbnail of {"__content__"=>"Rapid isolation and characterization of microsatellites in the critically endangered mountain bongo ().", "i"=>{"__content__"=>"Tragelaphus eurycerus isaaci"}}

Journal of genetics, 2018

High-throughput sequencing tools promise to revolutionize many aspects of genetic research, e.g. ... more High-throughput sequencing tools promise to revolutionize many aspects of genetic research, e.g. by allowing the identification of functional adaptive genetic variation. However, the expense and expertise required to apply these tools to basic conservation questions is a challenge for applications outside academia, resulting in a so-called 'conservation genomics gap' (Shafer . 2015). The conservation genetics paradigm is that, basic information about inbreeding and gene flow are often critical to inform conservation management of small populations (Ouborg . 2010). This information is often needed quickly and ideally should be accessible to workers without special expertise in genomics (DeSalle and Amato 2004). While the inferential power of highthroughput sequencing to interrogate the genome is profound, the cost for population analysis is higher (though decreasing) than for traditional neutral markers. Thus, the use of neutral markers is still relevant in conservation appli...

Research paper thumbnail of Rapid isolation and characterization of microsatellites from the genome of Asian arowana (Scleropages formosus, Osteoglossidae, Pisces)

Molecular Ecology, 2000

ABSTRACT

Research paper thumbnail of Multi‐individual Microsatellite identification: a multiple genome approach to microsatellite design (MiMi)

Molecular Ecology Resources, Aug 27, 2019

Research paper thumbnail of Using integrated population modelling in conservation monitoring: A case study in the common dormouse (Muscardinus avellanarius)

Research paper thumbnail of After the Ice Age: The Impact of Post-Glacial Dispersal on the Phylogeography of a Small Mammal, Muscardinus avellanarius

Research paper thumbnail of Developmental role of acetylcholinesterase in impulse control in zebrafish

Frontiers in behavioral neuroscience, 2015

Cellular and molecular processes that mediate individual variability in impulsivity, a key behavi... more Cellular and molecular processes that mediate individual variability in impulsivity, a key behavioral component of many neuropsychiatric disorders, are poorly understood. Zebrafish heterozygous for a nonsense mutation in ache (ache (sb55/+)) showed lower levels of impulsivity in a 5-choice serial reaction time task (5-CSRTT) than wild type and ache(+∕+). Assessment of expression of cholinergic (nAChR), serotonergic (5-HT), and dopamine (DR) receptor mRNA in both adult and larval (9 dpf) ache (sb55/+) revealed significant downregulation of chrna2, chrna5, and drd2 mRNA in ache (sb55/+) larvae, but no differences in adults. Acute exposure to cholinergic agonist/antagonists had no effect on impulsivity, supporting the hypothesis that behavioral effects observed in adults were due to lasting impact of developmental alterations in cholinergic and dopaminergic signaling. This shows the cross-species role of cholinergic signaling during brain development in impulsivity, and suggests zebraf...

Research paper thumbnail of The utility of zebrafish to study the mechanisms by which ethanol affects social behavior and anxiety during early brain development

Exposure to moderate levels of ethanol during brain development has a number of effects on social... more Exposure to moderate levels of ethanol during brain development has a number of effects on social behavior but the molecular mechanisms that mediate this are not well understood. Gaining a better understanding of these factors may help to develop therapeutic interventions in the future. Zebrafish offer a potentially useful model in this regard. Here, we introduce a zebrafish model of moderate prenatal ethanol exposure. Embryos were exposed to 20 mM ethanol for seven days (48hpf–9dpf) and tested as adults for individual social behavior and shoaling. We also tested their basal anxiety with the novel tank diving test. We found that the ethanol-exposed fish displayed reductions in social approach and shoaling, and an increase in anxiety in the novel tank test. These behavioral differences corresponded to differences in hrt1aa, slc6a4 and oxtr expression. Namely, acute ethanol caused a spike in oxtr and ht1aa mRNA expression, which was followed by down-regulation at 7dpf, and an up-regulation in slc6a4 at 72hpf. This study confirms the utility of zebrafish as a model system for studying the molecular basis of developmental ethanol exposure. Furthermore, it proposes a putative developmental mechanism characterized by ethanol-induced OT inhibition leading to suppression of 5-HT and up-regulation of 5-HT1A, which leads, in turn, to possible homeostatic up-regulation of 5-HTT at 72hpf and subsequent imbalance of the 5-HT system.

Research paper thumbnail of Development and implementation of a three-choice serial reaction time task for zebrafish ( Danio rerio)

Behavioural Brain Research, 2000

Zebrafish are an established and widely utilized developmental genetic model system, but limitati... more Zebrafish are an established and widely utilized developmental genetic model system, but limitations in developed behavioral assays have meant that their potential as a model in behavioral neuroscience has yet to be fully realized. Here, we describe the development of a novel operant behavioral assay to examine a variety of aspects of stimulus control in zebrafish using a 3 choice

Research paper thumbnail of Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood

Addiction Biology, 2014

Exposure to alcohol during early central nervous system development has been shown variously to a... more Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning.

Research paper thumbnail of Housing conditions differentially affect physiological and behavioural stress responses of zebrafish, as well as the response to anxiolytics

PloS one, 2012

Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advan... more Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advances in our understanding of zebrafish behaviour, their utility as a comparative model in behavioural neuroscience is beginning to be realised. One widely reported behavioural measure is the novel tank-diving assay, which has been often cited as a test of anxiety and stress reactivity. Despite its wide utilisation, and various validations against anxiolytic drugs, reporting of pre-test housing has been sparse in the literature. As zebrafish are a shoaling species, we predicted that housing environment would affect their stress reactivity and, as such, their response in the tank-diving procedure. In our first experiment, we tested various aspects of housing (large groups, large groups with no contact, paired, visual contact only, olfactory contact only) and found that the tank diving response was mediated by visual contact with conspecifics. We also tested the basal cortisol levels of grou...

Research paper thumbnail of The utility of zebrafish to study the mechanisms by which ethanol affects social behavior and anxiety during early brain development

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014

Research paper thumbnail of Discrimination reversal and attentional sets in zebrafish (Danio rerio)

Behavioural Brain Research, 2012

The potential of zebrafish as a comparative model in behavioural neuroscience is currently hamper... more The potential of zebrafish as a comparative model in behavioural neuroscience is currently hampered only by the lack of reliable and validated behavioural assays available to researchers. In the present experiment, we describe the performance of zebrafish in a test of attentional set formation. The fish were initially trained on a two-choice colour discrimination. Upon reaching acquisition criterion, the reinforced alternative was switched to the previously unreinforced alternative. Again, upon reaching criterion, the cues were replaced with a novel pair of colours (intra-dimensional shift) and reversed again on reaching criteria. We found that zebrafish show a steady decrease in trials-to-criteria over the four phases of the experiment, suggesting that they are forming and maintaining an attentional set, as has previously been demonstrated with mammals. Reversal learning deficits have been implicated in a variety of human psychological disorders (e.g., disorders of impulse control) and as such, we propose that performance of zebrafish in this procedure may represent a useful comparative model to complement existing rodent models.