Impulsive choices in mice lacking imprinted Nesp55

Genomic imprinting is the process whereby germline epigenetic events lead to parent‐of‐origin specific monallelic expression of a number of key mammalian genes. The imprinted gene Nesp is expressed from the maternal allele only and encodes for Nesp55 protein. In the brain, Nesp55 is found predominately in discrete areas of the hypothalamus and midbrain. Previously, we have shown that loss of Nesp55 gives rise to alterations in novelty‐related behaviour. Here, we extend these findings and demonstrate, using the Nesp^m/+ mouse model, that loss of Nesp55 leads to impulsive choices as measured by a delayed‐reinforcement task, whereby Nesp^m/+ mice were less willing to wait for a delayed, larger reward, preferring instead to choose an immediate, smaller reward. These effects were highly specific as performance in another component of impulsive behaviour, the ability to stop a response once started as assayed in the stop‐signal reaction time task, was equivalent to controls. We also showed changes in the serotonin system, a key neurotransmitter pathway mediating impulsive behaviour. First, we demonstrated that Nesp55 is co‐localized with serotonin and then went on to show that in midbrain regions there were reductions in mRNA expression of the serotonin‐specific genes Tph2 and Slc6a4, but not the dopamine‐specific gene Th in Nesp^m/+ mice; suggesting an altered serotonergic system could contribute, in part, to the changes in impulsive behaviour. These data provide a novel mode of action for genomic imprinting in the brain and may have implications for pathological conditions characterized by maladaptive response control.     

Physiological reactivity to infant crying: a behavioral genetic study

In this study, we examined adults' cardiac reactivity to repeated infant cry sounds in a genetically informative design. Three episodes of cry stimuli were presented to a sample of 184 adult twin pairs. Cardiac reactivity increased with each cry episode, indicating that subjects were increasingly sensitized to repeated infant distress signals. Non‐parents showed more cardiac reactivity than parents, and males displayed a larger increase in heart rate (HR) in response to repeated cry sounds than females. Multivariate genetic modeling showed that the genetic component of adults' HR while listening to infant crying was substantial. Genetic factors explained 37–51% of the variance in HR and similar genes influenced HR at baseline and HR reactivity to infant crying. The remaining variance in HR across the cry paradigm was accounted for by unique environmental influences (including measurement error). These results point to genetic and experiential effects on HR reactivity to infant crying that may contribute to the explanation of variance in sensitive and harsh parenting.     

Understanding behavioral responses of fish to pheromones in natural freshwater environments

There is an abundance of experimental studies and reviews that describe odorant-mediated behaviors of fish in laboratory microcosms, but research in natural field conditions has received considerably less attention. Fish pheromone studies in laboratory settings can be highly productive and allow for controlled experimental designs; however, laboratory tanks and flumes often cannot replicate all the physical, physiological and social contexts associated with natural environments. Field experiments can be a critical step in affirming and enhancing understanding of laboratory discoveries and often implicate the ecological significance of pheromones employed by fishes. When findings from laboratory experiments have been further tested in field environments, often different and sometimes contradictory conclusions are found. Examples include studies of sea lamprey (Petromyzon marinus) mating pheromones and fish alarm substances. Here, we review field research conducted on fish pheromones and alarm substances, highlighting the following topics: (1) contradictory results obtained in laboratory and field experiments, (2) how environmental context and physiological status influences behavior, (3) challenges and constraints of aquatic field research and (4) innovative techniques and experimental designs that advance understanding of fish chemical ecology through field research.     

Caenorhabditis elegans OSR-1 regulates behavioral and physiological responses to hyperosmotic environments

The molecular mechanisms that enable multicellular organisms to sense and modulate their responses to hyperosmotic environments are poorly understood. Here, we employ Caenorhabditis elegans to characterize the response of a multicellular organism to osmotic stress and establish a genetic screen to isolate mutants that are osmotic stress resistant (OSR). In this study, we describe the cloning of a novel gene, osr-1, and demonstrate that it regulates osmosensation, adaptation, and survival in hyperosmotic environments. Whereas wild-type animals exposed to hyperosmotic conditions rapidly lose body volume, motility, and viability, osr-1(rm1) mutant animals maintain normal body volume, motility, and viability even upon chronic exposures to high osmolarity environments. In addition, osr-1(rm1) animals are specifically resistant to osmotic stress and are distinct from previously characterized osmotic avoidance defective (OSM) and general stress resistance age-1(hx546) mutants. OSR-1 is expressed in the hypodermis and intestine, and expression of OSR-1 in hypodermal cells rescues the osr-1(rm1) phenotypes. Genetic epistasis analysis indicates that OSR-1 regulates survival under osmotic stress via CaMKII and a conserved p38 MAP kinase signaling cascade and regulates osmotic avoidance and resistance to acute dehydration likely by distinct mechanisms. We suggest that OSR-1 plays a central role in integrating stress detection and adaptation responses by invoking multiple signaling pathways to promote survival under hyperosmotic environments.     

Human behavioral influences and milk quality control programs

Mastitis is a major disease affecting the herds of dairy farmers worldwide. One of the indicators directly related to the widespread infection of this disease in herds is the bulk tank somatic cell count (BTSCC). Recent studies have shown that one of the risk factors associated with mastitis is the human factor. Therefore, understanding the influence of humans is essential to control and prevent the disease. The main goal of this study was to determine whether the motivations and barriers perceived by farmers could explain the variation in the BTSCC. This study was conducted at 75 dairy farms in southern Brazil. In the interviews with farmers, a survey based on Likert scale items was used to collect data. Structural equation models were used to explain the subjectivity in the ratio of observed variables and latent variables elucidating the possible causal relationships between the variables. The model indicated that some of the variation in the BTSCC can be explained by the farmer’s behavior, which is elucidated by his/her motivations and barriers. The correlations between motivations and the BTSCC and between barriers and the BTSCC were positive. These findings suggest that variations in the BTSCC can be explained by the motivations and barriers perceived by farmers and that the Fogg Behavior Model used in this study can be used to explain how human behaviors influence mastitis control. This study also indicates that consulting companies focused on improving milk quality should pay attention to the human factor to reduce these barriers.     

Beta-amyloid peptide influences behavioral plasticity in terrestrial snail

Influence of neurotoxic fragment of beta-amyloid peptide (25-35) on Helix lucorum behavioral plasticity (sensitization and food-aversion learning) was investigated. After beta-amyloid peptide (25-35) injection a significant reduction of behavioral long-term sensitization was observed. It was found, that beta-amyloid peptide (25-35) may interfere with associative learning and memory. Our results clearly demonstrate that beta-amyloid peptide (25-35) may play a significant role in behavioral plasticity by chronically eliminating certain underlying forms of synaptic plasticity.     

Larval damselflies in extreme environments: behavioral and physiological response to hypoxic stress

The extensive papyrus (Cyperus papyrus) swamps of East and Central Africa form a habitat of great ecological importance due to their extent, the extreme and chronic hypoxia of the interior swamp, and the unique assemblages of water-breathing insects that characterize these communities, including zygopteran (damselfly) larvae. The major goal of this study was to quantify physiological and behavioral responses of gilled and gill-less damselfly larvae of a papyrus swamp specialist, Proischnura subfurcatum, to low-oxygen conditions. Gill autotomization was common in P. subfurcatum of the Rwembaita Swamp in Kibale National Park, Uganda, with one to three gills missing from 56% of the specimens surveyed. We examined behavioral (ventilation activity and vertical migration) and physiological (metabolic rate) response to hypoxia in gilled and gill-less P. subfurcatum. Behavioral response to progressive hypoxia indicated that gill-less individuals rely more on use of wing sheaths (lifting and spreading) than gilled P. subfurcatum larvae. However, both morphs migrated to the surface to gain contact with atmospheric air under extreme hypoxia. On average, the rate of oxygen consumption of gill-less individuals was 51% lower than that of gilled individuals. This observed metabolic depression in gill-less P. subfurcatum may be attributed to the loss of major respiratory appendages. However, the apparent ability of both gilled and gill-less individuals to maintain their metabolic rates to a similar critical tension suggests other mechanisms may compensate for loss of gills, though not enough to mediate metabolic depression.     

Duration of hormonal deprivation: influences on physiological and behavioral responsiveness to estradiol

A total of 54 ovariectomized female guinea pigs were divided into three groups and tested six times at 2-week intervals for their responsiveness to exogenous ovarian hormones (3 days of 4 micrograms/kg estradiol benzoate plus 1 day of 0.4 mg/kg progesterone) or control injections (0.2 ml oil vehicle). Two weeks after ovariectomy, treatment with estradiol significantly reduced food intake and body weight, and also produced vaginal membrane rupture in 98.1% of the females. When tested for sexual behavior at 4, 6, and 8 hr after the progesterone injection, 29 of the subjects (53.7%) displayed lordosis in response to manual stimulation. Twelve weeks after ovariectomy, the effects of estradiol on food intake, body weight, and vaginal membrane condition had not diminished. However, the overall proportion of females from which lordosis could be elicited declined to 27.8%. Biweekly injections of estradiol benzoate plus progesterone to one of the groups of females did not prevent this decline in the sexual response. Based on these results, it was concluded that the observed reduction in behavioral lordosis does not represent a general decline in the responsiveness of ovariectomized guinea pigs to estrogenic stimulation, but may involve changes in their responsiveness to progesterone or in other mechanisms more specifically associated with sexual behavior.     

A novel photosynthetic strategy for adaptation to low-iron aquatic environments

Iron (Fe) availability is a major limiting factor for primary production in aquatic environments. Cyanobacteria respond to Fe deficiency by derepressing the isiAB operon, which encodes the antenna protein IsiA and flavodoxin. At nanomolar Fe concentrations, a PSI-IsiA supercomplex forms, comprising a PSI trimer encircled by two complete IsiA rings. This PSI-IsiA supercomplex is the largest photosynthetic membrane protein complex yet isolated. This study presents a detailed characterization of this complex using transmission electron microscopy and ultrafast fluorescence spectroscopy. Excitation trapping and electron transfer are highly efficient, allowing cyanobacteria to avoid oxidative stress. This mechanism may be a major factor used by cyanobacteria to successfully adapt to modern low-Fe environments.     

Use of novel objects to enhance environments of captive chimpanzees

A small group of chimpanzees was allowed to manipulate different quantities of novel objects in order to enhance their captive conditions. This procedure led to a general increase in the manipulation frequency by the apes. It decreased their inactivity and their self-grooming, and almost eliminated the abnormal behaviors displayed by one individual. The distribution of novel objects did not affect the total frequency of social interactions and did not increase the aggressivity of the animals, even though dominant individuals secured most of the objects when only a small number of them were available. Following their familiarization with the novel objects, the chimpanzees' manipulation frequency decreased whereas self-grooming and abnormal behaviors were increased. Suggestions are made on how to maximize the use of a limited bank of toys to occupy captive chimpanzees.     

Winter space use of coyotes in high-elevation environments: behavioral adaptations to deep-snow landscapes

In the last century, coyotes (Canis latrans) have expanded their range geographically, but have also expanded their use of habitats within currently occupied regions. Because coyotes are not morphologically adapted for travel in deep snow, we studied coyote space use patterns in a deep-snow landscape to examine behavioral adaptations enabling them to use high elevations during winter. We examined the influence of snow depth, snow penetrability, canopy cover, and habitat type, as well as the rates of prey and predator track encounters, on coyote travel distance in high-elevation terrain in northwestern Wyoming, USA. We backtracked 13 radio-collared coyotes for 265.41 km during the winters of 2006–2007 and 2007–2008, and compared habitat use and movement patterns of the actual coyotes with 259.11 km of random travel paths. Coyotes used specific habitats differently than were available on the landscape. Open woodlands were used for the majority of coyote travel distance, followed by mixed conifer, and closed-stand spruce–fir. Prey track encounters peaked in closed-stand, mature Douglas fir, followed by 50- to 150-year-old lodgepole pine stands, and 0- to 40-year-old regeneration lodgepole pine stands. Snowmobile trails had the most variation between use and availability on the landscape (12.0 % use vs. 0.6 % available). Coyotes increased use of habitats with dense canopy cover as snow penetration increased and rates of rodent and red squirrel track encounters increased. Additionally, coyotes spent more time in habitats containing more tracks of ungulates. Conversely, use of habitats with less canopy cover decreased as snow depth increased, and coyotes traveled more directly in habitats with less canopy cover and lower snow penetration, suggesting coyotes used these habitats to travel. Coyotes persisted throughout the winter and effectively used resources despite deep snow conditions in a high-elevation environment.     

A novel vein graft model: adaptation to differential flow environments

Accelerated intimal hyperplasia in response to altered flow environment is critical to the process of vein bypass graft failure. Lack of a reproducible animal model for dissecting the mechanisms of vein graft (VG) remodeling has limited progress toward solving this clinically significant problem. Combining a cuffed anastomotic technique with other surgical manipulations, we developed a well-defined, more robust method for studying hemodynamic factors in VG arterialization. VG with fistula placement, complete occlusion, or partial distal branch ligation (DBL) was performed in the carotid artery of 56 rabbits. Extensive hemodynamic and physiological analyses were performed to define the hemodynamic forces and histological adaptations of the wall at 1-28 days. Anastomotic time averaged 12 min, with 100% patency of bilateral grafts and unilateral grafts plus no adjunct or delayed fistula. Bilateral VG-DBL resulted in an immediate disparity in wall shear (0.8 +/- 0.1 vs. 12.4 +/- 1.1 dyn/cm2, ligated vs. contralateral graft). Grafts exposed to low shear stress responded primarily through enhanced intimal thickening (231 +/- 35 vs. 36 +/- 18 microm, low vs. high shear). High-shear-stress grafts adapted through enhanced outward remodeling, with a 24% increase in lumen diameter at 28 days (3.0 +/- 0.1 vs. 3.7 +/- 0.2 mm, low vs. high shear). We have taken advantage of the cuffed anastomotic technique and combined it with a bilateral VG-DBL model to dissect the impact of hemodynamic forces on VG arterialization. This novel model offers a robust, clinically relevant, statistically powerful small animal model for evaluation of high- and low-shear-regulated VG remodeling.     

Gonadal influences on behavioral deterioration with aging of male rats

There is much evidence that gonadal steroids modulate brain and behavioral development. However their possible influence on age-related deteroriation of brain and behavior has received little attention. We now present evidence that neonatal castration reduces the decline in locomotion, motor coordination, and circadian activity rhythms that normally accompanies old age in male rats. Three behavioral tests (open field, Rota-Rod, and wheel running) were conducted with aged male rats (24 months). Those castrated in the first 24 hr of postnatal life were more active in the open field (P less than 0.001) than aged rats that were sham-operated neonatally. The sham-operated aged males showed a more marked deterioration of motor coordination in the Rota-Rod (P less than 0.01) and greater disorganization of circadian wheel-running (P less than 0.05) than the neonatal castrates or than young rats neonatally sham-operated.     

High-content behavioral analysis of Caenorhabditis elegans in precise spatiotemporal chemical environments

To quantitatively understand chemosensory behaviors, it is desirable to present many animals with repeatable, well-defined chemical stimuli. To that end, we describe a microfluidic system to analyze Caenorhabditis elegans behavior in defined temporal and spatial stimulus patterns. A 2 cm × 2 cm structured arena allowed C. elegans to perform crawling locomotion in a controlled liquid environment. We characterized behavioral responses to attractive odors with three stimulus patterns: temporal pulses, spatial stripes and a linear concentration gradient, all delivered in the fluid phase to eliminate variability associated with air-fluid transitions. Different stimulus configurations preferentially revealed turning dynamics in a biased random walk, directed orientation into an odor stripe and speed regulation by odor. We identified both expected and unexpected responses in wild-type worms and sensory mutants by quantifying dozens of behavioral parameters. The devices are inexpensive, easy to fabricate, reusable and suitable for delivering any liquid-borne stimulus.     

T cell receptor alpha-chain influences reactivity to Mls-1 in V beta 8.1 transgenic mice.

Most, but not all, V beta 8.1+ T cells respond to M1s-1 and are clonally deleted in the thymus of M1s-1-expressing animals. To formally examine the role of the TCR alpha-chain in reactivity and tolerance to M1s-1, we have analyzed M1s-1 reactivity in a large panel of CD4+ hybridomas generated from TCR V beta 8.1 transgenic mice, that express an identical, potentially M1s-1-reactive beta-chain. The data show that the alpha-chain strongly influences the M1s-1 reactivity of the hybridomas and that the differences in reactivity had relevance for tolerance. Thus, V alpha 11+ hybridiomas were biased toward M1s-1 reactivity and V alpha 11+ T cells were correspondingly absent from the peripheral repertoire of M1s-1-expressing transgenic mice. V alpha 2+ hybridomas, on the other hand, were biased against M1s-1 reactivity, and V alpha 2+ T cells were correspondingly amplified in the M1s-1-expressing transgenic mice. Structural analysis of the alpha-chains revealed that the M1s-1 reactivity of the V alpha 11+ hybridomas segregated precisely with family member, such that V alpha 11.1+ hybridomas were M1s-1-reactive and V alpha 11.3+ hybridomas were not M1s-1-reactive. On the other hand, there was not a clear correlation between family member and M1s-1 reactivity in the V alpha 2+ hybridomas. The hybridomas also showed striking variation in their reactivity to staphylococcal enterotoxin B (SEB), and the SEB reactivity of the V alpha 11+ hybridomas correlated precisely with family member and with M1s-1 reactivity. In contrast, there was not a clear correlation with V alpha 2+ alpha-chain structure and SEB reactivity. Also, there was no correlation between M1s-1 reactivity and SEB reactivity in individual V alpha 2+ hybridomas, suggesting that the recognition of the two superantigens by the same TCR is not equivalent. Taken together, these data define a role for the TCR alpha-chain in superantigen reactivity and T cell tolerance, and provide a structural explanation for the different fates of M1s-1-reactive T cells in normal and transgenic mice.     

Immune and behavioral consequences of microglial reactivity in the aged brain

Bidirectional communication between the immune system and the brain is essential for mounting the appropriate immunological, physiological, and behavioral responses to immune activation. Aging, however, may impair this important bi-directional interaction. In support of this notion, peripheral infection in the elderly is associated with an increased frequency of behavioral and cognitive complications. Recent findings in animal models of aging and neurodegenerative disease indicate that microglia, innate immune cells of the brain, become primed or reactive. Understanding age- and disease-associated alterations in microglia is important because glia (microglia and astrocytes) play an integral role in propagating inflammatory signals that are initiated in the periphery. In this capacity, brain glia produce inflammatory cytokines that target neuronal substrates and elicit a sickness-behavior syndrome that is normally beneficial to the host organism. Increased reactivity of microglia sets the stage for an exaggerated neuroinflammatory cytokine response following activation of the peripheral innate immune system, which may underlie subsequent long-lasting behavioral and cognitive deficits. In support of this premise, recent findings indicate that stimulation of the peripheral immune system in aged rodents causes exaggerated neuroinflammation that is paralleled by cognitive impairment, prolonged sickness, and depressive-like complications. Therefore, the purpose of this review is to discuss the new evidence that age-associated priming of microglia could play a pathophysiological role in exaggerated behavioral and cognitive sequelae to peripheral infection.     

Genetic influences on behavioral inhibition and anxiety in juvenile rhesus macaques

In humans and other animals, behavioral responses to threatening stimuli are an important component of temperament. Among children, extreme behavioral inhibition elicited by novel situations or strangers predicts the subsequent development of anxiety disorders and depression. Genetic differences among children are known to affect risk of developing behavioral inhibition and anxiety, but a more detailed understanding of genetic influences on susceptibility is needed. Nonhuman primates provide valuable models for studying the mechanisms underlying human behavior. Individual differences in threat-induced behavioral inhibition (freezing behavior) in young rhesus monkeys are stable over time and reflect individual levels of anxiety. This study used the well-established human intruder paradigm to elicit threat-induced freezing behavior and other behavioral responses in 285 young pedigreed rhesus monkeys. We examined the overall influence of quantitative genetic variation and tested the specific effect of the serotonin transporter promoter repeat polymorphism. Quantitative genetic analyses indicated that the residual heritability of freezing duration (behavioral inhibition) is h ² = 0.384 ( P  = 0.012) and of 'orienting to the intruder' (vigilance) is h ² = 0.908 ( P  = 0.00001). Duration of locomotion and hostility and frequency of cooing were not significantly heritable. The serotonin transporter polymorphism showed no significant effect on either freezing or orienting to the intruder. Our results suggest that this species could be used for detailed studies of genetic mechanisms influencing extreme behavioral inhibition, including the identification of specific genes that are involved in predisposing individuals to such behavior.