Browsing by Author "Hamilton, Trevor"
Now showing 1 - 20 of 40
Results Per Page
Sort Options
Item Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness(2016) Hamilton, Trevor; Kwan, Garfield T.; Gallup, Joshua; Tresguerres, MartinAggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab.Item The amnestic agent anisomycin disrupts intrinsic membrane properties of hippocampal neurons via a loss of cellular energetics(2019) Scavuzzo, C. J.; LeBlancq, M. J.; Nargang, F.; Lemieux, H.; Hamilton, Trevor; Dickson, C. T.The nearly axiomatic idea that de novo protein synthesis is necessary for long-term memory consolidation is based heavily on behavioral studies using translational inhibitors such as anisomycin. Although inhibiting protein synthesis has been shown to disrupt the expression of memory, translational inhibitors also have been found to profoundly disrupt basic neurobiological functions, including the suppression of ongoing neural activity in vivo. In the present study, using transverse hippocampal brain slices, we monitored the passive and active membrane properties of hippocampal CA1 pyramidal neurons using intracellular whole cell recordings during a brief ~30-min exposure to fast-bath-perfused anisomycin. Anisomycin suppressed protein synthesis to 46% of control levels as measured using incorporation of radiolabeled amino acids and autoradiography. During its application, anisomycin caused a significant depolarization of the membrane potential, without any changes in apparent input resistance or membrane time constant. Anisomycin-treated neurons also showed significant decreases in firing frequencies and spike amplitudes, and showed increases in spike width across spike trains, without changes in spike threshold. Because these changes indicated a loss of cellular energetics contributing to maintenance of ionic gradients across the membrane, we confirmed that anisomycin impaired mitochondrial function by reduced staining with 2,3,5-triphenyltetrazolium chloride and also impaired cytochrome c oxidase (complex IV) activity as indicated through high-resolution respirometry. These findings emphasize that anisomycin-induced alterations in neural activity and metabolism are a likely consequence of cell-wide translational inhibition. Critical reevaluation of studies using translational inhibitors to promote the protein synthesis dependent idea of long-term memory is absolutely necessary. NEW & NOTEWORTHY Memory consolidation is thought to be dependent on the synthesis of new proteins because translational inhibitors produce amnesia when administered just after learning. However, these agents also disrupt basic neurobiological functions. We show that blocking protein synthesis disrupts basic membrane properties of hippocampal neurons that correspond to induced disruptions of mitochondrial function. It is likely that translational inhibitors cause amnesia through their disruption of neural activity as a result of dysfunction of intracellular energetics.Item Analysis of the potential behavioral impact of methanol when used as a solvent: Dataset from zebrafish (Danio rerio) behavioral research(2021) Hamilton, Trevor; Szaszkiewicz, Joshua; Krook, Jeffrey T.; Burggren, WarrenToxicants are commonly administered to experimental organisms using solvents as vehicles. One common vehicle for dissolving toxicants is methanol (CH3OH), a solvent which on its own is capable of altering physiology and behavior high concentrations. This dataset describes behavioral results in zebrafish (Danio rerio) individually exposed to methanol (0.25%, 2.5% vol/vol), or control water, for 30 min prior to behavioral testing. Zebrafish were placed into an open field arena to examine locomotion and zone preference, which was recorded and quantified with motion-tracking software (EthoVision XT). Time spent in the outer (“thigmotaxis”) zone of the arena is a proxy for increased anxiety-like behavior in zebrafish. Additionally, a novel object was placed into the center of the arena to quantify relative increases in boldness/exploration between the methanol and control groups. There were no differences in time spent in any zone of the arena or distance travelled between either group, in either test.Item The anti-epileptic actions of neuropeptide Y in the hippocampus are mediated by Y2 and not Y5 receptors(2005) El Bahh, Bouchaïb; Balosso, Silvia; Hamilton, Trevor; Herzog, Herbert; Beck-Sickinger, Annette; Sperk, Günther; Gehlert, Donald; Vezzani, AnnamariaNeuropeptide Y (NPY) potently inhibits glutamate release and seizure activity in rodent hippocampus in vitro and in vivo, but the nature of the receptor(s) mediating this action is controversial. In hippocampal slices from rats and several wild-type mice, a Y2-preferring agonist mimicked, and the Y2-specific antagonist BIIE0246 blocked, the NPY-mediated inhibition both of glutamatergic transmission and of epileptiform discharges in two different slice models of temporal lobe epilepsy, stimulus train-induced bursting (STIB) and 0-Mg2+ bursting. Whereas Y5 receptor-preferring agonists had small but significant effects in vitro, they were blocked by BIIE0246, and a Y5 receptor-specific antagonist did not affect responses to any agonist tested in any preparation. In slices from inline image mice, NPY was without effect on evoked potentials or in either of the two slice seizure models. In vivo, intrahippocampal injections of Y2- or Y5-preferring agonists inhibited seizures caused by intrahippocampal kainate, but again the Y5 agonist effects were insensitive to a Y5 antagonist. Neither Y2- nor Y5-preferring agonists affected kainate seizures in inline image mice. A Y5-specific antagonist did not displace the binding of two different NPY ligands in WT or inline image mice, whereas all NPY binding was eliminated in the inline image mouse. Thus, we show that Y2 receptors alone mediate all the anti-excitatory actions of NPY seen in the hippocampus, whereas our findings do not support a role for Y5 receptors either in vitro or in vivo. The results suggest that agonists targeting the Y2 receptor may be useful anticonvulsants.Item Behavioural responses of the hagfish Eptatretus stoutii to nutrient and noxious stimuli(2019) Glover, Chris N.; Newton, Dustin; Bejwa, Jasmin; Goss, Greg G.; Hamilton, TrevorThe suitability of a traditional testing paradigm (e.g. choice chamber) for assessing chemosensory behaviour in the Pacific hagfish, Eptatretus stoutii, was examined. Actively-swimming hagfish, tested at night, showed no preference for any region of a T-maze in the absence of a stimulus, but in the presence of an olfactory food cue, spent significantly more time in the zone where the cue was placed. Conversely, hagfish avoided spending time in the zone the fish anaesthetic 3-amino benzoic acid ethylester (MS-222) was placed, and demonstrated significantly more reversal responses in which the fish moved its body backwards. These data suggest that hagfish are an amenable model species for laboratory testing of behaviour.Item Chondroitin Sulphate acts as an 'alarm cue' in zebrafish(2020) Bajwa, Jasmin; Hamilton, TrevorZebrafish are conspecific organisms that are sensitive to the use of ‘alarm cues’, a procedure in behavioural fish research used to create experimental stress responses. We used a commercially available chemical compound, chondroitin sulphate, extracted from shark cartilage, as the possible ‘alarm cue’. This chemical compound controls for standardization errors common with alarm cues extracted from individual fish. We conducted an open field test, followed by a novel object approach test, to assess the behavioural responses consequential of 30 minutes of chondroitin sulphate exposure at different concentrations (ie. 1, 10, and 100 mg/L). Secondly, we locally applied 250 μL of 100 mg/L of chondroitin sulphate to the centre of an open field arena, and again assessed behavioural responses. The time individual fish spent in the centre, transition, and thigmotaxis zones was examined, along with the distance each fish moved and the time spent immobile. There was a significant increase in the time fish spent in the thigmotaxis zone during the novel object approach test after chondroitin sulphate exposure. We also found that fish in the experimental group spent more time in the thigmotaxis zone following the injection of chondroitin sulphate, compared to fish in the control group. These findings suggest this compound can be used as a reliable alarm cue stimulus in zebrafish.Item CO2-induced ocean acidification increases anxiety in rockfish via alteration of GABAA receptor functioning(2013) Hamilton, Trevor; Holcombe, Adam; Tresguerres, MartinThe average surface pH of the ocean is dropping at a rapid rate due to the dissolution of anthropogenic CO2, raising concerns for marine life. Additionally, some coastal areas periodically experience upwelling of CO2-enriched water with reduced pH. Previous research has demonstrated ocean acidification (OA)-induced changes in behavioural and sensory systems including olfaction, which is due to altered function of neural gamma-aminobutyric acid type A (GABAA) receptors. Here, we used a camera-based tracking software system to examine whether OA-dependent changes in GABAA receptors affect anxiety in juvenile Californian rockfish (Sebastes diploproa). Anxiety was estimated using behavioural tests that measure light/dark preference (scototaxis) and proximity to an object. After one week in OA conditions projected for the next century in the California shore (1125 ± 100 µatm, pH 7.75), anxiety was significantly increased relative to controls (483 ± 40 µatm CO2, pH 8.1). The GABAA-receptor agonist muscimol, but not the antagonist gabazine, caused a significant increase in anxiety consistent with altered Cl− flux in OA-exposed fish. OA-exposed fish remained more anxious even after 7 days back in control seawater; however, they resumed their normal behaviour by day 12. These results show that OA could severely alter rockfish behaviour; however, this effect is reversible.Item Coho salmon are behaviourally resilient after 120 days of rearing under altered photoperiods and salinities(2020) Szaszkiewicz, Joshua; Hamilton, Trevor; Krook, Jeffrey T.; Richards, Jeffrey G.; Stiller, Kevin; Brauner, Colin J.; Hamilton, TrevorRecirculating aquaculture systems (RAS) are a sustainable method used in aquaculture to farm healthy stocks of fish intended for market. In order to optimize fish growth, environmental conditions within RAS, including salinity and photoperiod are manipulated. However, little is known about the effect of varying photoperiod and salinity on behaviour. In this study, Coho salmon (Oncorhynchus kisutch) smolts were reared in RAS for 120 days on either a 12 hour light: 12h dark or 24 hour light photoperiod and in salinities of either 2.5, 5, or 10 ppt. An additional group reared in 30 ppt and 24h light was examined. To determine the impact of photoperiod and salinity on behaviour, three behavioural test assays were employed. Locomotion was quantified using an open field test, the novel object approach test was used to quantify boldness, and the light/dark test was used to quantify anxiety-like behaviour. In the open field test we observed no significant differences in locomotion. In the novel object approach test, the 2.5 ppt (12h/12h) group demonstrated decreased boldness relative to the 10 ppt (24h) and 30 ppt (24h) groups. In the light/dark test, the 2.5 (12h/12h) group spent significantly less time in the dark zone. However, no significant differences were observed between any of the treatment groups, suggesting that anxiety-like behaviour was only minimally impacted. Taken together, the photoperiods and salinities investigated did not significantly affect coho salmon behaviour, which has important implications for RAS aquaculture.Item Continuous light (relative to a 12:12 photoperiod) has no effect on anxiety-like behaviour, boldness, and locomotion in coho salmon (Oncorhynchus kisutch) post-smolts in recirculating aquaculture systems at a salinity of either 2.5 or 10 ppt(2022) Hamilton, Trevor; Szaszkiewicz, Joshua; Krook, Jeffrey T.; Richards, Jeffrey G.; Stiller, Kevin; Brauner, Colin J.There is increased interest in rearing salmon in Recirculating Aquaculture Systems (RAS), where environmental conditions can be tightly controlled to optimize growth. Photoperiod and salinity are two important parameters that can be manipulated in RAS. A longer photoperiod permits more time for feeding, while intermediate salinities may reduce the energetic costs of ionoregulation, both of which may enhance growth. However, little is known about how rearing at different photoperiods and salinity affect behaviour, an understudied but important research topic for intensive fish rearing. To address this, we examined the behavioural effects of two salinities and two photoperiod regimes in coho salmon (Oncorhynchus kisutch) post-smolts reared continuously for 120 days in a RAS. Fish were reared on a photoperiod of either 12 h light:12 h dark (12:12), or 24 h light (24:0) at salinities of 2.5 and 10 ppt. To investigate behavioural differences associated with these treatments, we quantified: i) movement in an open-field test, ii) exploratory behaviour/boldness using a novel object approach test, and iii) anxiety-like behaviour with a light/dark test. The 24:0 groups displayed no differences in boldness/anxiety-like behaviour and locomotion relative to the 12:12 groups at their respective salinities. Taken together, fish reared under continuous light (24:0) show negligible behavioural alterations compared to fish reared under normal light dark conditions (12:12).Item Dopamine modulates synaptic plasticity in dendrites of rat and human dentate granule cells(2010) Hamilton, Trevor; Wheatley, Matthew; Sinclair, Barry; Bachmann, Madeline; Larkum, Matthew; Colmers, WilliamThe mechanisms underlying memory formation in the hippocampal network remain a major unanswered aspect of neuroscience. Although high-frequency activity appears essential for plasticity, salience for memory formation is also provided by activity in ventral tegmental area (VTA) dopamine projections. Here, we report that activation of dopamine D1 receptors in dentate granule cells (DGCs) can preferentially increase dendritic excitability to both high-frequency afferent activity and high-frequency trains of backpropagating action potentials. Using whole-cell patch clamp recordings, calcium imaging, and neuropeptide Y to inhibit postsynaptic calcium influx, we found that activation of dendritic voltage-dependent calcium channels (VDCCs) is essential for dopamine-induced long-term potentiation (LTP), both in rat and human dentate gyrus (DG). Moreover, we demonstrate previously unreported spike-timing–dependent plasticity in the human hippocampus. These results suggest that when dopamine is released in the dentate gyrus with concurrent high-frequency activity there is an increased probability that synapses will be strengthened and reward-associated spatial memories will be formed.Item The dose makes the poison: non-linear behavioural response to CO2-induced aquatic acidification in zebrafish (Danio rerio)(2021) Hamilton, Trevor; Hurst Radke, Nicole; Bajwa, Jasmin; Chaput, Shayna; Tresguerres, MartinCO2-induced aquatic acidification is predicted to affect fish neuronal GABAA receptors leading to widespread behavioural alterations. However, the large variability in the magnitude and direction of behavioural responses suggests substantial species-specific CO2 threshold differences, life history and parental acclimation effects, experimental artifacts, or a combination of these factors. As an established model organism, zebrafish (Danio rerio) can be reared under stable conditions for multiple generations, which may help control for some of the variability observed in wild-caught fishes. Here, we used two standardized tests to investigate the effect of 1-week acclimatization to four pCO2 levels on zebrafish anxiety-like behaviour, exploratory behaviour, and locomotion. Fish acclimatized to 900 μatm CO2 demonstrated increased anxiety-like behaviour compared to control fish (~480 μatm), however, the behaviour of fish exposed to 2200 μatm CO2 was indistinguishable from that of controls. In addition, fish acclimatized to 4200 μatm CO2 had decreased anxiety-like behaviour; i.e. the opposite response than the 900 μatm CO2 treatment. On the other hand, exploratory behaviour did not differ among any of the pCO2 exposures that were tested. Thus, zebrafish behavioural responses to elevated pCO2 are not linear; with potential important implications for physiological, environmental, and aquatic acidification studies.Item Effects of acute exposure to cannabinoids on zebrafish behaviour(2018) Pinder, Lyndsay; Schalomon, Melike; Hamilton, TrevorCannabinoid therapeutic potential is increasingly studied using animal models. Zebrafish (Danio rerio) are a useful model organism because cannabinoids interrupt zebrafish endocannabinoid systems similarly to how human endocannabinoid systems are interrupted (Oltrabella, Melgoza, Nguyen, & Guo, 2017). Zebrafish also demonstrate observable behavioural changes when under stress. Zebrafish behaviour in response to multiple doses of the cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), will be recorded. Finally, dose response curves for the effects of THC and CBD on behaviour during the light/dark preference and novel tank dive tests will be established. Both of these tests are tests of anxiety displayed by individual zebrafish, and both are linked to predator avoidance behaviours. Previous research has suggested that THC and CBD may have anxiolytic effects (Stewart, Kaleuff, 2013; Nazario et al., 2015), implying these cannabinoids may alter zebrafish fish behaviour during the tests, as compared to zebrafish in the control condition.Item Effects of ocean acidification on dopamine-mediated behavioral responses of a coral reef damselfish(2023) Hamilton, Trevor; Tresguerres, Martin; Kwan, Garfield T.; Szaszkiewicz, Joshua; Franczak, Brian C.; Cyronak, Tyler; Andersson, Andreas J.; Kline, David I.We investigated whether CO2-induced ocean acidification (OA) affects dopamine receptor-dependent behavior in bicolor damselfish (Stegastes partitus). Damselfish were kept in aquaria receiving flow through control (pH ~ 8.03; pCO2 ~ 384 μatm) or OA (pH ~ 7.64; CO2 ~ 1100 μatm) seawater at a rate of 1 L min−1. Despite this relatively fast flow rate, fish respiration further acidified the seawater in both control (pH ~7.88; pCO2 ~ 595 μatm) and OA (pH ~7.55; pCO2 ~ 1450 μatm) fish-holding aquaria. After five days of exposure, damselfish locomotion, boldness, anxiety, and aggression were assessed using a battery of behavioral tests using automated video analysis. Two days later, these tests were repeated following application of the dopamine D1 receptor agonist SKF 38393. OA-exposure induced ceiling anxiety levels that were significantly higher than in control damselfish, and SKF 38393 increased anxiety in control damselfish to a level not significantly different than that of OA-exposed damselfish. Additionally, SKF 38393 decreased locomotion and increased boldness in control damselfish but had no effect in OA-exposed damselfish, suggesting an alteration in activity of dopaminergic pathways that regulate behavior under OA conditions. These results indicate that changes in dopamine D1 receptor function affects fish behavior during exposure to OA. However, subsequent measurements of seawater sampled using syringes during the daytime (~3–4 pm local time) from crevasses in coral reef colonies, which are used as shelter by damselfish, revealed an average pH of 7.73 ± 0.03 and pCO2 of 925.8 ± 62.2 μatm; levels which are comparable to Representative Concentration Pathway (RCP) 8.5 predicted end-of-century mean OA levels in the open ocean. Further studies considering the immediate environmental conditions experienced by fish as well as individual variability and effect size are required to understand potential implications of the observed OA-induced behavioral effects on damselfish fitness in the wild.Item Effects of super-class cannabis terpenes beta-caryophyllene and alpha-pinene on zebrafish behavioural biomarkers(2022) Johnson, Andrea; Stewart, Alycia; El-Hakim, Ismaeel; Hamilton, TrevorTerpenes possess a wide range of medicinal properties and are potential therapeutics for a variety of pathological conditions. This study investigated the acute effects of two cannabis terpenes, β-caryophyllene and α-pinene, on zebrafish locomotion, anxiety-like, and boldness behaviour using the open field exploration and novel object approach tests. β-caryophyllene was administered in 0.02%, 0.2%, 2.0%, and 4% doses. α-pinene was administered in 0.01%, 0.02%, and 0.1% doses. As α-pinene is a racemic compound, we also tested its (+) and (−) enantiomers to observe any differential effects. β-caryophyllene had only a sedative effect at the highest dose tested. α-pinene had differing dose-dependent effects on anxiety-like and motor variables. Specifically, (+)-α-pinene and (−)-α-pinene had significant effects on anxiety measures, time spent in the thigmotaxis (outer) or center zone, in the open field test, as well as locomotor variables, swimming velocity and immobility. (+ /−)-α-pinene showed only a small effect on the open field test on immobility at the 0.1% dose. This study demonstrates that α-pinene can have a sedative or anxiolytic effect in zebrafish and may have different medicinal properties when isolated into its (+) or (−) enantiomers.Item Episodic-like memory in zebrafish(2016) Hamilton, Trevor; Myggland, Allison; Duperreault, Erika; May, Zacnicte; Gallup, Joshua; Powell, Russell A.; Schalomon, Melike; Digweed, ShannonEpisodic-like memory tests often aid in determining an animal's ability to recall the what, where, and which (context) of an event. To date, this type of memory has been demonstrated in humans, wild chacma baboons, corvids (Scrub jays), humming birds, mice, rats, Yucatan minipigs, and cuttlefish. The potential for this type of memory in zebrafish remains unexplored even though they are quickly becoming an essential model organism for the study of a variety of human cognitive and mental disorders. Here we explore the episodic-like capabilities of zebrafish ( Danio rerio) in a previously established mammalian memory paradigm. We demonstrate that when zebrafish were presented with a familiar object in a familiar context but a novel location within that context, they spend more time in the novel quadrant. Thus, zebrafish display episodic-like memory as they remember what object they saw, where they saw it (quadrant location), and on which occasion (yellow or blue walls) it was presented.Item Establishing zebrafish as a model to study the anxiolytic effects of scopolamine(2017) Hamilton, Trevor; Morrill, Adam; Lucas, Kayla; Gallup, Joshua; Harris, Megan; Healey, Meghan; Pitman, Taylor; Schalomon, Melike; Digweed, Shannon; Tresguerres, MartinScopolamine (hyoscine) is a muscarinic acetylcholine receptor antagonist that has traditionally been used to treat motion sickness in humans. However, studies investigating depressed and bipolar populations have found that scopolamine is also effective at reducing depression and anxiety symptoms. The potential anxiety-reducing (anxiolytic) effects of scopolamine could have great clinical implications for humans; however, rats and mice administered scopolamine showed increased anxiety in standard behavioural tests. This is in direct contrast to findings in humans, and complicates studies to elucidate the specific mechanisms of scopolamine action. The aim of this study was to assess the suitability of zebrafish as a model system to test anxiety-like compounds using scopolamine. Similar to humans, scopolamine acted as an anxiolytic in individual behavioural tests (novel approach test and novel tank diving test). The anxiolytic effect of scopolamine was dose dependent and biphasic, reaching maximum effect at 800 µM. Scopolamine (800 µM) also had an anxiolytic effect in a group behavioural test, as it significantly decreased their tendency to shoal. These results establish zebrafish as a model organism for studying the anxiolytic effects of scopolamine, its mechanisms of action and side effects.Item Examining behavioural test sensitivity and locomotor proxies of anxiety-like behaviour in zebrafish(2023) Johnson, Andrea; Loh, Erica; Slessor, Jordan; Verbitsky, Ryan; Franczak, Brian C.; Schalomon, Melike; Hamilton, TrevorThis study assessed the sensitivity of four anxiety-like behaviour paradigms in zebrafish: the novel tank dive test, shoaling test, light/dark test, and the less common shoal with novel object test. A second goal was to measure the extent to which the main effect measures are related to locomotor behaviours to determine whether swimming velocity and freezing (immobility) are indicative of anxiety-like behaviour. Using the well-established anxiolytic, chlordiazepoxide, we found the novel tank dive to be most sensitive followed by the shoaling test. The light/dark test and shoaling plus novel object test were the least sensitive. A principal component analysis and a correlational analysis also showed the locomotor variables, velocity and immobility, did not predict the anxiety-like behaviours across all behaviour tests.Item Exposure to bloom-like concentrations of two marine Synechococcus cyanobacteria (strains CC9311 and CC9902) differentially alters fish behaviour(2014) Hamilton, Trevor; Paz-Yepes, Javier; Morrison, Rachel M.; Palenik, Brian; Tresguerres, MartinCoastal California experiences large-scale blooms of Synechococcus cyanobacteria, which are predicted to become more prevalent by the end of the 21st century as a result of global climate change. This study investigated whether exposure to bloom-like concentrations of two Synechococcus strains, CC9311 and CC9902, alters fish behaviour. Black perch (Embiotoca jacksoni) were exposed to Synechococcus strain CC9311 or CC9902 (1.5 × 106 cells ml−1) or to control seawater in experimental aquaria for 3 days. Fish movement inside a testing arena was then recorded and analysed using video camera-based motion-tracking software. Compared with control fish, fish exposed to CC9311 demonstrated a significant preference for the dark zone of the tank in the light–dark test, which is an indication of increased anxiety. Furthermore, fish exposed to CC9311 also had a statistically significant decrease in velocity and increase in immobility and they meandered more in comparison to control fish. There was a similar trend in velocity, immobility and meandering in fish exposed to CC9902, but there were no significant differences in behaviour or locomotion between this group and control fish. Identical results were obtained with a second batch of fish. Additionally, in this second trial we also investigated whether fish would recover after a 3 day period in seawater without cyanobacteria. Indeed, there were no longer any significant differences in behaviour among treatments, demonstrating that the sp. CC9311-induced alteration of behaviour is reversible. These results demonstrate that blooms of specific marine Synechococcus strains can induce differential sublethal effects in fish, namely alterations light–dark preference behaviour and motility.Item Modulation of distal calcium electrogenesis by neuropeptide Y1 receptors inhibits neocortical long-term depression(2013) Hamilton, Trevor; Xapelli, Sara; Michaelson, Sheldon; Larkum, Matthew; Colmers, WilliamIn layer 5 neocortical pyramidal neurons, backpropagating action potentials (bAPs) firing at rates above a critical frequency (CF) induce supralinear Ca2+ influx and regenerative potentials in apical dendrites. Paired temporally with an EPSP, this Ca2+ influx can result in synaptic plasticity. We studied the actions of neuropeptide Y (NPY), an abundant neocortical neuropeptide, on Ca2+ influx in layer 5 pyramidal neurons of somatosensory neocortex in Sprague Dawley and Wistar rats, using a combination of somatic and dendritic intracellular recordings and simultaneous Ca2+ imaging. Ca2+ influx induced by trains of bAPs above a neuron's CF was inhibited by NPY, acting only at the distal dendrite, via Y1 receptors. NPY does not affect evoked synaptic glutamate release, paired synaptic facilitation, or synaptic rundown in longer trains. Extracellular Cs+ did not prevent NPY's postsynaptic effects, suggesting it does not act via either G-protein-activated inwardly rectifying K+ conductance (GIRK) or hyperpolarization-activated, cyclic nucleotide-gated channels. NPY application suppresses the induction of the long-term depression (LTD) normally caused by pairing 100 EPSPs with bursts of 2 bAPs evoked at a supracritical frequency. These findings suggest that distal dendritic Ca2+ influx is necessary for LTD induction, and selective inhibition of this distal dendritic Ca2+ influx by NPY can thus regulate synaptic plasticity in layer 5 pyramidal neurons.Item Neurodevelopmental and metabolomic responses from prenatal coexposure to perfluorooctanesulfonate (PFOS) and methylmercury (MeHg) in Sprague-Dawley rats(2019) Reardon, Anthony J. F.; Karathra, Jacqueline; Ribbenstedt, Anton; Benskin, Jonathan P.; MacDonald, Amy M.; Kinniburgh, David W.; Hamilton, Trevor; Fouad, Karim; Martin, Jonathan W.Methylmercury (MeHg) and perfluorooctanesulfonate (PFOS) are major contaminants of human blood that are both common in dietary fish, thereby raising questions about their combined impact on human development. Here, pregnant Sprague–Dawley rats ingested a daily dose, from gestational day 1 through to weaning, of either 1 mg/kg bw PFOS (PFOS-only), 1 mg/kg MeHg (MeHg-only), a mixture of 0.1 mg/kg PFOS and 1 mg/kg MeHg (Low-Mix), or of 1 mg/kg of PFOS and 1 mg/kg MeHg (High-Mix). Newborns were monitored for physical milestones and reflexive developmental responses, and in juveniles the spontaneous activity, anxiety, memory, and cognition were assessed. Targeted metabolomics of 199 analytes was applied to sectioned brain regions of juvenile offspring. Newborns in the High-Mix group had decreased weight gain as well as delayed reflexes and innate behavioral responses compared to controls and individual chemical groups indicating a toxicological interaction on early development. In juveniles, cumulative mixture effects increased in a dose-dependent manner in tests of anxiety-like behavior. However, other developmental test results suggested antagonism, as PFOS-only and MeHg-only juveniles had increased hyperactivity and thigmotaxic behavior, respectively, but fewer effects in Low-Mix and High-Mix groups. Consistent with these behavioral observations, a pattern of antagonism was also observed in neurochemicals measured in rat cortex, as PFOS-only and MeHg-only juveniles had altered concentrations of metabolites (e.g., lipids, amino acids, and biogenic amines), while no changes were evident in the combined exposures. The cortical metabolites altered in PFOS-only and MeHg-only exposed groups are involved in inhibitory and excitatory neurotransmission. These proof-of-principle findings at relatively high doses indicate the potential for toxicological interaction between PFOS and MeHg, with developmental-stage specific effects. Future mixture studies at lower doses are warranted, and prospective human birth cohorts should consider possible confounding effects from PFOS and mercury exposure on neurodevelopment.