Among-population variance of phenotypic traits is of high relevance for understanding evolutionar... more Among-population variance of phenotypic traits is of high relevance for understanding evolutionary mechanisms that operate in relatively short timescales, but various sources of nonindependence, such as common ancestry and gene flow, can hamper the interpretations. In this comparative analysis of 138 dog breeds, we demon-O RCI D
The intestinal tract affects the brain through metabolites produced by gut-inhabiting bacteria. I... more The intestinal tract affects the brain through metabolites produced by gut-inhabiting bacteria. In this study, we show that the number of errors the dogs commit in a short-term memory test and also their age is linked to the gut microbiome composition. The proportion of Fusobacteria is lower in older animals. Dogs with better memory performance (i.e., fewer mistakes) have relatively fewer Actinobacteria in their fecal samples collected right after the behavior test. This result is in agreement with the high abundance of some Actinobacteria in the gastrointestinal tract of persons living with Alzheimer's disease. Links between memory performance and gut microbiota have been reported on rodents but not on dogs before. The research opens up new venues in canine aging and neurodevelopmental research.
Background and aims: Dogs have recently become an important model species for comparative social ... more Background and aims: Dogs have recently become an important model species for comparative social and cognitive neuroscience. Brain template-related label maps are essential for functional magnetic resonance imaging (fMRI) data analysis, to localize neural responses. In this study, we present a detailed, individual-based, T1-weighted MRI-based brain label map used in dog neuroimaging analysis. Methods: A typical, medium-headed dog (a 7.5-year-old male Golden Retriever) was selected from a cohort of 22 dogs, based on brain morphology (shape, size, and gyral pattern), to serve as the template for a label map. Results: Eighty-six 3-dimensional labels were created to highlight the main cortical (cerebral gyri on the lateral and medial side) and subcortical (thalamus, caudate nucleus, amygdala, and hippocampus) structures of the prosencephalon and diencephalon, and further main parts of brainstem (mesencephalon and rhombencephalon). Discussion: Importantly, this label map is (a) considerably more detailed than any available dog brain template; (b) it is easy to use with freeware and commercial neuroimaging software for MRI and fMRI analysis; and (c) it can be registered to other existing templates, including a recent average-based dog brain template. Using the coordinate system and label map proposed here can enhance precision and standard localization during future canine neuroimaging studies.
In humans, age-related changes in personality occur in a non-random fashion with respect to their... more In humans, age-related changes in personality occur in a non-random fashion with respect to their direction, timing, and magnitude. In dogs, there are still gaps in our knowledge about the detailed dynamics of age-related personality changes. We analysed the personality of 217 Border collies aged from 0.5 to 15 years both cross-sectionally and longitudinally using a test battery, to specify age periods when changes most prominently occur, assess the magnitude of changes, and analyse individual differences in personality change. We found that similar to humans, changes in personality occur unevenly during the dogs' life course, however, their dynamics seems to be specific for each trait. Activity-independence decreased mostly from puppyhood (0.5-1 years) to adolescence (> 1-2 years), then continued to decrease in a slowing rate. Novelty seeking did not change markedly until middle age (> 3-6 years), then showed a steady linear decrease. Problem orientation increased strongly until middle age then showed no marked changes in later age periods. We also revealed individual differences in personality change over time, and showed that a few individuals with potential age-related impairments significantly affected the general age trajectory of some traits. These results raise caution against the over-generalisation of global age trends in dogs.
In dogs, the social and spatial restriction associated with living in a kennel environment could ... more In dogs, the social and spatial restriction associated with living in a kennel environment could lead to chronic stress and the development of abnormal behaviors ("kennel-dog syndrome"). However, little is known about how kenneled dogs differ from their conspecifics living as pets in human families. In the current study, using a test battery exposing the dogs to novel stimuli, we compared the behavior of three groups of beagles: (1) kenneled dogs living in a restricted environment with limited human contact (N = 78), (2) family dogs living in human families as pets (N = 37), and (3) adopted dogs born in the kenneled population but raised in human families (N = 13). We found one factor comprising most of the test behaviors, labeled as Responsiveness. Family dogs and adopted dogs scored higher in Responsiveness than kenneled dogs. However, 23% of the kenneled dogs were comparable to family and adopted dogs based on a cluster analysis, indicating a similar (positive) reaction to novel stimuli, while 77% of the kenneled dogs were unresponsive (mostly immobile) in at least part of the test. To assess if the behavioral difference between the family and kenneled dogs could be due to genetic divergence of these two populations and/or to lower genetic diversity of the kenneled dogs, we analyzed their genetic structure using 11 microsatellite markers. We found no significant difference between the populations in their genetic diversity (i.e., heterozygosity, level of inbreeding), nor any evidence that the family and kenneled populations originated from different genetic pools. Thus, the behavior difference between the groups more likely reflects a G × E interaction, that is, the influence of specific genetic variants manifesting under specific environmental conditions (kennel life). Nevertheless, some kenneled individuals were (genetically) more resistant to social and environmental deprivation. Selecting for such animals could strongly improve the welfare of kenneled dog populations. Moreover, exploring the genetic background of their higher resilience could also help to better understand the genetics behind stress-and fear-related behaviors.
Introduction: The aim of this study was to explore spontaneous social interactions between dyads ... more Introduction: The aim of this study was to explore spontaneous social interactions between dyads of unfamiliar adult dogs. Although intraspecific encounters are frequent events in the life of pet dogs, the factors that might influence encounters, such as sex, dyad composition, reproductive status, age, and state of cohabitation (keeping the dogs singly or in groups), remained unexplored. Methods: In this study, we assigned unfamiliar, non-aggressive dogs to three types of dyads defined by sex and size. We observed their unrestrained, spontaneous behaviors in an unfamiliar dog park, where only the two dogs, the owners, and experimenter were present. Results: We found that the dogs, on average, spent only 17% of the time (less than 1 min) in proximity. Sex, dyad composition, reproductive status, and age influenced different aspects of the interactions in dyads. Female dogs were more likely to initiate the first contact in their dyad but later approached the partner less frequently, were less likely to move apart, and displayed less scent marking. Following and moving apart were more frequent in male-male interactions. Neutered dogs spent more time following the other dog and sniffed other dogs more frequently. The time companion dogs spent in proximity and number of approaches decreased with age. Conclusion: The study provides guidance for dog owners about the outcomes of intraspecific encounters based on the dog's age, sex, and reproductive status, as well as the sex of the interacting partner.
Non-REM bursts of activity in the sigma range (9-16 Hz) typical of sleep spindles predict learnin... more Non-REM bursts of activity in the sigma range (9-16 Hz) typical of sleep spindles predict learning in dogs, similar to humans and rats. Little is known, however, about the age-related changes in amplitude, density (spindles/minute) and frequency (waves/second) of canine spindles. We investigated a large sample (N = 155) of intact and neutered pet dogs of both sexes, varying in breed and age, searching for spindles in segments of non-REM sleep. We recorded EEG from both a frontal midline electrode (Fz) and a central midline electrode (Cz) in 55.5% of the dogs, in the remaining animals only the Fz electrode was active (bipolar derivation). A similar topography was observed for fast (≥13 Hz) spindle occurrence as in humans (fast spindle number, density on Cz > Fz). For fast spindles, density was higher in females, and increased with age. These effects were more pronounced among intact animals and on Fz. Slow spindle density declined and fast spindle frequency increased with age on Cz, while on Fz age-related amplitude decline was observed. The frequency of fast spindles on Fz and slow spindles on Cz was linked to both sex and neutering, suggesting modulation by sexual hormones. Intact females displayed higher frequencies than males and neutered females. Our findings support the argument that sigma bursts in the canine non-REM sleep are analogous to human sleep spindles, and suggest that slow and fast spindles display different trajectories related to age, of which an increase in frontal fast spindles is unique to dogs. The sleeping brain shows various patterns of activity that predict awake performance in the domains of memory and cognitive ability 1 . Several of these oscillatory activities are also altered in the aging process 2 , which makes sleep physiology an attractive target for studying cognitive aging in humans and animal models. The dog has been suggested to be a suitable model for human cognitive aging . Their advantage over rodents in this respect is argued on the basis of a more similar behavioural repertoire 6 and a shared environment 7 . Recently sleep physiology in dogs has received growing attention due to the development of a non-invasive polysomnographic method 8 which opens up a possibility for integrating the study of cognitive aging and sleep in pet dogs. The sleep spindle, which appears as a short (0.5-5 seconds) train of rhythmic and symmetric waves , traceable with EEG and occurring predominantly during non-REM sleep, had been described, but seldom quantified in the dog. Various contradicting accounts about its defining features in canines had been published based on visual inspection alone 8,14-16 , derived from both invasive and non-invasive work. Using criteria for automatic sleep spindle detection previously validated in humans 17 we were able to show that transients in the sigma range (9-16 Hz), characteristic of the human sleep spindle, show a similar association with post-sleep recall of novel information, i.e. dogs with higher learning gain displayed more spindles/minute 18 . The sleep spindle is a particularly attractive target of investigation with regard to aging. Its rate of occurrence (density), amplitude, frequency (waves/second of a single spindle) and duration have each been found to change in humans, from childhood to puberty , from young adult to old age , and between healthy and pathologically aging groups . Age-related changes, in particular those associated with cognitive decline, are characterized by decreased density (spindles/minute) and amplitude . A subset of studies also found an increase in spindle frequency for older subjects 2 , whereas adolescent development is characterized by increased density . A distinction between fast and slow spindles is common in humans . The two sub-types can be topographically distinguished. Fast spindles are predominantly found in central and posterior derivations and oscillate on average ≥13 Hz, whereas slow spindles (≤13 Hz) are predominant in the frontal derivations. The distinction is, however, less clear based on the origin of spindles. Invasive work in cats had originally implied
Tanulmányunkban a 2018 tavaszán készült Fiatal kutatók Magyarországon című felmérés legfőbb eredm... more Tanulmányunkban a 2018 tavaszán készült Fiatal kutatók Magyarországon című felmérés legfőbb eredményeit foglaljuk össze. A tudományos pálya választásában a fiatalok legfőbb motivációját a felfedezés izgalma és a tudományos elhivatottság jelenti. Ez a kezdeti lelkesedés azonban, mely a tevékenység jellegéből természetes módon fakad, és mindenfajta aktív tudománypolitikai stratégia nélkül is megjelenik, önmagában nem elegendő a kutatók hoszszú távú szakmai fejlődéséhez és magánéleti boldogulásához. Kérdőívünk válaszadói számos olyan problémára hívják fel a figyelmet, melyek azonnali kezelést igényelnek. A fiatalok tudományos pályán maradását elsősorban a személyes anyagi nehézségek, a kutatási források hiánya és a nem kiszámítható, nem tervezhető szakmai karrier nehezítik meg, leginkább tehát ezeken a területeken van szükség beavatkozásra ahhoz, hogy a hazai tudományos pálya vonzóvá váljon és az is maradjon a fiatalok számára.
Dominance is well defined in ethology, debated in psychology, and is often unclear among the dog ... more Dominance is well defined in ethology, debated in psychology, and is often unclear among the dog owning public and in the press. However, to date, no study has examined how owners perceive dominance in dogs, and what different behaviours and personality types are used to describe dominant and subordinate individuals. A questionnaire study was launched to investigate the external validity of owner-derived estimates of dominance in dog dyads sharing the same household (N = 1,151). According to the owners, dogs rated as dominant (87%) have priority access to resources (resting place, food, and rewards), undertake certain tasks (defend and lead the group, bark more), display dominance (win fights, lick the other's mouth less, and mark over the other's urine), share certain personality traits (smarter, more aggressive and impulsive), and are older than their partner dog (all p < 0.0001). An age-related hypothesis has been suggested to explain dominance in dogs; but we found that dog age did not explain the occurrence of dominance related behaviours over the owners' estimate of dominance status. Results suggest that owner-derived reports of dominance ranks of dogs living in multi-dog households correspond to ethologically valid behavioural markers of dominance. Size and physical condition were unrelated to the perceived dominance. Surprisingly, in mixed-sex dyads, females were more frequently rated as dominant than males, which might correspond to a higher proportion of neutered females in this subgroup. For future studies that wish to allocate dominance status using owner report, we offer a novel survey.
Aging research has experienced a burst of scientific efforts in the last decades as the growing r... more Aging research has experienced a burst of scientific efforts in the last decades as the growing ratio of elderly people has begun to pose an increased burden on the healthcare and pension systems of developed countries. Although many breakthroughs have been reported in understanding the cellular mechanisms of aging, the intrinsic and extrinsic factors that contribute to senescence on higher biological levels are still barely understood. The dog, Canis familiaris, has already served as a valuable model of human physiology and disease. The possible role the dog could play in aging research is still an open question, although utilization of dogs may hold great promises as they naturally develop age-related cognitive decline, with behavioral and histological characteristics very similar to those of humans. In this regard, family dogs may possess unmatched potentials as models for investigations on the complex interactions between environmental, behavioral, and genetic factors that determine the course of aging. In this review, we summarize the known genetic pathways in aging and their relevance in dogs, putting emphasis on the yet barely described nature of certain aging pathways in canines. Reasons for highlighting the dog as a future aging and gerontology model are also discussed, ranging from its unique evolutionary path shared with humans, its social skills, and the fact that family dogs live together with their owners, and are being exposed to the same environmental effects.
Most common methods that directly show macro-or microscopic anatomy of the brain usually require ... more Most common methods that directly show macro-or microscopic anatomy of the brain usually require the removal of the organ from the neurocranium. However, the brain can be revealed in situ by using proper sectioning techniques. Our aim was to both improve the cryosectioning method, test its limits and create a high-resolution macro-anatomical image series of a Beagle brain, which at the time of the study did not exist. A two-year-old female Beagle has been scanned with CT and MRI ante and post mortem, then the arteries of the head were filled with red resin. After freezing to -80˚C, a neurocranium block was created and was embedded into a water-gelatin mix. Using a special milling device and a DSLR camera, 1112 consecutive RGB-color cryosections were made with a 100 μm layer thickness and captured in high resolution (300 dpi, 24-bit color, and pixel size was 19.5 x 19.5 μm). Image post-processing was done with Adobe Photoshop CS3 and Thermo Scientific Amira 6.0 softwares, and as a result of the proper alignment and coregistration, visualization and comparing was possible with all the applied imaging modalities (CT, MRI, cryosectioning) in any arbitrary plane. Surface models from the arteries, veins, brain and skull were also generated after segmentation in the same coordinate system, giving a unique opportunity for comparing the two-dimensional and three-dimensional anatomy. This is the first study which focuses directly to this high-definition multimodal visualization of the canine brain, and it provides the most accurate results compared to previous cryosectioning studies, as using an improved method, higher image quality, more detailed image, proper color fidelity and lower artefact formation were achieved. Based on the methodology we described, it can serve as a base for future multimodal (CT, MR, augmented-or virtual reality) imaging atlases for medical, educational and scientific purposes.
Dogs living on Bali Island have been free-ranging for thousands of years. A large group of expatr... more Dogs living on Bali Island have been free-ranging for thousands of years. A large group of expatriates sometimes adopt Bali dogs and keep them restricted to their houses and backyards, as is typical in modern western cultures. This provides us with the unique opportunity to compare the personality traits of dogs to their lifestyle either living as human companions or as free-ranging animals, exploring at the same time the impact of demographic variables (such as age, sex, and neutered status) on personality. After controlling for internal consistency of the scales and between-observer variation, we found that free-ranging Bali dogs were rated as less active, less excitable, less aggressive towards animals, and less inclined to chase animals or humans than Bali dogs living as human companions. Among free-ranging dogs, females were found to be more excitable. Females in the whole sample were also more fearful of people. The results of this preliminary study suggest that a change in lifestyle, i.e. being adopted, and living in a confined environment has negative consequences on some canine personality traits, such as activity/excitability, aggression towards animals, and prey drive.
Cognitive aging in dogs has attracted interest due to their utility as an animal model for human ... more Cognitive aging in dogs has attracted interest due to their utility as an animal model for human aging and their need for veterinary care. The latter in particular would benefit substantially from standardized tests for fast and comfortable administration, which would reduce time and financial costs for both owners and practitioners. Here, we examine a battery of tests (the mini mental test, MMT) selected and adapted toward this end in a sample of 20 young (1-5y) and 26 old (10-15y) dogs. Each behavioral test was evaluated for its ability to discriminate between dogs based on their age category. Older dogs displayed less social interest, performed worse in a place-memory test, and seemed both less interested in and less fearful of a novel, moving object, aligning with previous findings and thus confirming the MMT's external validity. The older dogs were also less excitable, assessed by a dog personality questionnaire. Based on these results, for future studies comparing the behavior of young adult and old dogs, we suggest four feasible subtests (greeting, problem box, memory, novel object) that can be conducted outdoors, without complex devices, in a short time (< than 15 min), and evaluated on the spot. To determine which performance levels are within the normal range for old dogs, larger samples grouped by breed and age will need to be tested in future studies.
Background: Although the molecular function of wolframin remains unclear, the lack of this protei... more Background: Although the molecular function of wolframin remains unclear, the lack of this protein is known to cause stress in the endoplasmic reticulum. Some variants in the Wolfram Syndrome 1 gene (WFS1) were associated with various neuropsychiatric disorders in humans, such as aggressiveness, impulsivity and anxiety. Results: Here we present an in silico study predicting a single nucleotide polymorphism (rs852850348) in the canine WFS1 gene which was verified by direct sequencing and was genotyped by a PCR-based technique. We found that the rs852850348 polymorphism is located in a putative microRNA (cfa-miR-8834a and cfa-miR-1838) binding site. Therefore, the molecular effect of allelic variants was studied in a luciferase reporter system that allowed assessing gene expression. We demonstrated that the variant reduced the activity of the reporter protein expression in an allele-specific manner. Additionally, we performed a behavioral experiment and investigated the association with this locus to different performance in this test. Association was found between food possessivity and the studied WFS1 gene polymorphism in the Border collie breed. Conclusions: Based on our findings, the rs852850348 locus might contribute to the genetic risk of possessivity behavior of dogs in at least one breed and might influence the regulation of wolframin expression.
Visual and auditory impairments can have a large impact on performance in cognitive tests. It is ... more Visual and auditory impairments can have a large impact on performance in cognitive tests. It is important to evaluate the sensory capacities of dogs before enrolling them in cognitive tests, in order to exclude sensory impairment as confounding effect. Therefore we designed multiple non-invasive testing paradigms to detect subjects with potential auditory and visual impairment, without requiring extensive training for the dog. Multiple testing was a means to add internal reliability, and to reduce the risk of false positives due to habituation and previous learning or false negatives due to random errors. Our sensory test battery consisted of four subtests: (1) 'Clapping' auditory test, (2) 'Recorded sound' auditory test, (3) 'Distance' visual test, and (4) 'Darkness' visual test. The 'Clapping test' was similar to the clapping test used by veterinarians, with the addition that the clapping was performed at various distances from the dog. In the 'Recorded sound test', the dogs' reaction to various sounds played back at different volumes. In the 'Distance test' we placed a small piece of food on one of four plates placed on the grounds at varying distances from the dogs. In the 'Darkness test', we measured the dogs' performance in walking through an S-shaped route during artificial dusk and daylight-like conditions.
In the Methods section under subheading 'Subjects and Behavioural paradigm' . "15 adult pet dogs,... more In the Methods section under subheading 'Subjects and Behavioural paradigm' . "15 adult pet dogs, mean age ± SD: 3.67 ± 1.91; 8 males, 7 females; from 7 pure breeds (3 Border Collies, 2 Golden Retrievers, 1 Labrador Retriever, 1 Poodle, 1 Belgian Shepherd, 1 Puli, 1 Miniature Schnauzer) and 3 mixed breeds (3 unknown, 1 mixed Briard and 1 mixed Malinois), participated three times in 3-hour-long polysomnography recordings 3 , on a total of 3 days (see Fig. )".
Aging is the largest risk factor in many diseases and mortality alike. As the elderly population ... more Aging is the largest risk factor in many diseases and mortality alike. As the elderly population is expected to increase at an accelerating rate in the future, these phenomena will pose a growing socio-economic burden on societies. To successfully cope with this challenge, a deeper understanding of aging is crucial. In many aspects, the companion dog is an increasingly popular model organism to study aging, with the promise of producing results that are more applicable to humans than the findings that come from the studies of classical model organisms. In this preliminary study we used the whole-genome sequence of two extremely old dogs -age: 22 and 27 years (or 90-135% more, than the average lifespan of dogs) -in order to make the first steps to understand the genetic background of extreme longevity in dogs. We identified more than ∼80 1000 novel SNPs in the two dogs (7500 of which overlapped between them) when compared to three publicly available canine SNP databases, which included SNP information from850 dogs. Most novel mutations (∼52000 SNPs) were identified at non-coding regions, while 4.6% of the remaining SNPs (n∼1600) were at exons, including 670 missense variants -76 of which overlapped between the two animalsacross 472 genes. Based on their gene ontologies, these genes were related -among others -to gene transcription/translation and its regulation, to immune response and the nervous system in general. We also detected 12 loss-of-function mutations, although their actual effect is unclear. Several genetic pathways were also identified, which pathways may be tempting candidates to be investigated in large sample sizes in order to confirm their relevance in extreme longevity in dogs (and possibly, in humans). We hypothesize a possible link between extreme longevity and the regulation of gene transcription/translation, which hypothesis should be further investigated in the future. This phenomenon could define an interesting direction for future research aiming to better understand longevity. The presented preliminary results highlight the utility of the companion dog in the study of the genetic background of longevity and aging.
Several studies on age-related cognitive decline in dogs involve laboratory dogs and prolonged tr... more Several studies on age-related cognitive decline in dogs involve laboratory dogs and prolonged training. We developed two spatial tasks that required a single 1-h session. We tested 107 medium-large sized dogs: Byoung^(N=41, aged 2.5-6.5 years) and Bold^(N=66, aged 8-14.5 years). Our results indicated that, in a discrimination learning task and in a reversal learning task, young dogs learned significantly faster than the old dogs, indicating that these two tasks could successfully be used to investigate differences in spatial learning between young and old dogs. We also provide two novel findings. First, in the reversal learning, the dogs trained based on the location of stimuli learned faster than the dogs trained based on stimulus characteristics. Most old dogs did not learn the task within our cut-off of 50 trials. Training based on an object's location is therefore more appropriate for reversal learning tasks. Second, the contrast between the response to the positive and negative stimuli was narrower in old dogs, compared to young dogs, during the reversal learning task, as well as the cognitive bias test. This measure favors comparability between tasks and between studies. Following the cognitive bias test, we could not find any indication of differences in the positive and negative expectations between young and old dogs. Taken together, these findings do not support the hypothesis that old dogs have more negative expectations than young dogs and the use of the cognitive bias test in older dogs requires further investigation.
To describe the extent of age-related cognitive decline in dogs, information regarding the baseli... more To describe the extent of age-related cognitive decline in dogs, information regarding the baseline occurrence of associated behaviours in the general population is necessary. With a seven-item, data driven Age-Related Changes scale, we evaluated the relationship between sensory functions, training, sex, and the occurrence of behavioural signs associated with cognitive decline across the whole adult lifespan. The twofold difference in lifespan between small and large dogs presents challenges for ageing studies, with no widely accepted method to control for body size as it relates to chronological age and longevity, when comparing behavioural signs of cognitive decline. To address this issue, we utilized relative age, calculated using the estimated expected lifespan of the individuals in our questionnaire study. Signs of cognitive decline were already detectable in' Mature' dogs (at 50-75% of the expected lifespan). Visual, auditory and olfactory impairments all resulted in significantly higher scores on the Age-Related Changes scale. Participating in dog training activities was revealed to be protective against behavioural signs of cognitive decline in aged dogs as perceived by the owners. These results revealed possible beneficial effects of training on cognitive ageing and emphasize the importance of routinely screening the sensory capacities of ageing dogs. (D. Szabó).
Among-population variance of phenotypic traits is of high relevance for understanding evolutionar... more Among-population variance of phenotypic traits is of high relevance for understanding evolutionary mechanisms that operate in relatively short timescales, but various sources of nonindependence, such as common ancestry and gene flow, can hamper the interpretations. In this comparative analysis of 138 dog breeds, we demon-O RCI D
The intestinal tract affects the brain through metabolites produced by gut-inhabiting bacteria. I... more The intestinal tract affects the brain through metabolites produced by gut-inhabiting bacteria. In this study, we show that the number of errors the dogs commit in a short-term memory test and also their age is linked to the gut microbiome composition. The proportion of Fusobacteria is lower in older animals. Dogs with better memory performance (i.e., fewer mistakes) have relatively fewer Actinobacteria in their fecal samples collected right after the behavior test. This result is in agreement with the high abundance of some Actinobacteria in the gastrointestinal tract of persons living with Alzheimer's disease. Links between memory performance and gut microbiota have been reported on rodents but not on dogs before. The research opens up new venues in canine aging and neurodevelopmental research.
Background and aims: Dogs have recently become an important model species for comparative social ... more Background and aims: Dogs have recently become an important model species for comparative social and cognitive neuroscience. Brain template-related label maps are essential for functional magnetic resonance imaging (fMRI) data analysis, to localize neural responses. In this study, we present a detailed, individual-based, T1-weighted MRI-based brain label map used in dog neuroimaging analysis. Methods: A typical, medium-headed dog (a 7.5-year-old male Golden Retriever) was selected from a cohort of 22 dogs, based on brain morphology (shape, size, and gyral pattern), to serve as the template for a label map. Results: Eighty-six 3-dimensional labels were created to highlight the main cortical (cerebral gyri on the lateral and medial side) and subcortical (thalamus, caudate nucleus, amygdala, and hippocampus) structures of the prosencephalon and diencephalon, and further main parts of brainstem (mesencephalon and rhombencephalon). Discussion: Importantly, this label map is (a) considerably more detailed than any available dog brain template; (b) it is easy to use with freeware and commercial neuroimaging software for MRI and fMRI analysis; and (c) it can be registered to other existing templates, including a recent average-based dog brain template. Using the coordinate system and label map proposed here can enhance precision and standard localization during future canine neuroimaging studies.
In humans, age-related changes in personality occur in a non-random fashion with respect to their... more In humans, age-related changes in personality occur in a non-random fashion with respect to their direction, timing, and magnitude. In dogs, there are still gaps in our knowledge about the detailed dynamics of age-related personality changes. We analysed the personality of 217 Border collies aged from 0.5 to 15 years both cross-sectionally and longitudinally using a test battery, to specify age periods when changes most prominently occur, assess the magnitude of changes, and analyse individual differences in personality change. We found that similar to humans, changes in personality occur unevenly during the dogs' life course, however, their dynamics seems to be specific for each trait. Activity-independence decreased mostly from puppyhood (0.5-1 years) to adolescence (> 1-2 years), then continued to decrease in a slowing rate. Novelty seeking did not change markedly until middle age (> 3-6 years), then showed a steady linear decrease. Problem orientation increased strongly until middle age then showed no marked changes in later age periods. We also revealed individual differences in personality change over time, and showed that a few individuals with potential age-related impairments significantly affected the general age trajectory of some traits. These results raise caution against the over-generalisation of global age trends in dogs.
In dogs, the social and spatial restriction associated with living in a kennel environment could ... more In dogs, the social and spatial restriction associated with living in a kennel environment could lead to chronic stress and the development of abnormal behaviors ("kennel-dog syndrome"). However, little is known about how kenneled dogs differ from their conspecifics living as pets in human families. In the current study, using a test battery exposing the dogs to novel stimuli, we compared the behavior of three groups of beagles: (1) kenneled dogs living in a restricted environment with limited human contact (N = 78), (2) family dogs living in human families as pets (N = 37), and (3) adopted dogs born in the kenneled population but raised in human families (N = 13). We found one factor comprising most of the test behaviors, labeled as Responsiveness. Family dogs and adopted dogs scored higher in Responsiveness than kenneled dogs. However, 23% of the kenneled dogs were comparable to family and adopted dogs based on a cluster analysis, indicating a similar (positive) reaction to novel stimuli, while 77% of the kenneled dogs were unresponsive (mostly immobile) in at least part of the test. To assess if the behavioral difference between the family and kenneled dogs could be due to genetic divergence of these two populations and/or to lower genetic diversity of the kenneled dogs, we analyzed their genetic structure using 11 microsatellite markers. We found no significant difference between the populations in their genetic diversity (i.e., heterozygosity, level of inbreeding), nor any evidence that the family and kenneled populations originated from different genetic pools. Thus, the behavior difference between the groups more likely reflects a G × E interaction, that is, the influence of specific genetic variants manifesting under specific environmental conditions (kennel life). Nevertheless, some kenneled individuals were (genetically) more resistant to social and environmental deprivation. Selecting for such animals could strongly improve the welfare of kenneled dog populations. Moreover, exploring the genetic background of their higher resilience could also help to better understand the genetics behind stress-and fear-related behaviors.
Introduction: The aim of this study was to explore spontaneous social interactions between dyads ... more Introduction: The aim of this study was to explore spontaneous social interactions between dyads of unfamiliar adult dogs. Although intraspecific encounters are frequent events in the life of pet dogs, the factors that might influence encounters, such as sex, dyad composition, reproductive status, age, and state of cohabitation (keeping the dogs singly or in groups), remained unexplored. Methods: In this study, we assigned unfamiliar, non-aggressive dogs to three types of dyads defined by sex and size. We observed their unrestrained, spontaneous behaviors in an unfamiliar dog park, where only the two dogs, the owners, and experimenter were present. Results: We found that the dogs, on average, spent only 17% of the time (less than 1 min) in proximity. Sex, dyad composition, reproductive status, and age influenced different aspects of the interactions in dyads. Female dogs were more likely to initiate the first contact in their dyad but later approached the partner less frequently, were less likely to move apart, and displayed less scent marking. Following and moving apart were more frequent in male-male interactions. Neutered dogs spent more time following the other dog and sniffed other dogs more frequently. The time companion dogs spent in proximity and number of approaches decreased with age. Conclusion: The study provides guidance for dog owners about the outcomes of intraspecific encounters based on the dog's age, sex, and reproductive status, as well as the sex of the interacting partner.
Non-REM bursts of activity in the sigma range (9-16 Hz) typical of sleep spindles predict learnin... more Non-REM bursts of activity in the sigma range (9-16 Hz) typical of sleep spindles predict learning in dogs, similar to humans and rats. Little is known, however, about the age-related changes in amplitude, density (spindles/minute) and frequency (waves/second) of canine spindles. We investigated a large sample (N = 155) of intact and neutered pet dogs of both sexes, varying in breed and age, searching for spindles in segments of non-REM sleep. We recorded EEG from both a frontal midline electrode (Fz) and a central midline electrode (Cz) in 55.5% of the dogs, in the remaining animals only the Fz electrode was active (bipolar derivation). A similar topography was observed for fast (≥13 Hz) spindle occurrence as in humans (fast spindle number, density on Cz > Fz). For fast spindles, density was higher in females, and increased with age. These effects were more pronounced among intact animals and on Fz. Slow spindle density declined and fast spindle frequency increased with age on Cz, while on Fz age-related amplitude decline was observed. The frequency of fast spindles on Fz and slow spindles on Cz was linked to both sex and neutering, suggesting modulation by sexual hormones. Intact females displayed higher frequencies than males and neutered females. Our findings support the argument that sigma bursts in the canine non-REM sleep are analogous to human sleep spindles, and suggest that slow and fast spindles display different trajectories related to age, of which an increase in frontal fast spindles is unique to dogs. The sleeping brain shows various patterns of activity that predict awake performance in the domains of memory and cognitive ability 1 . Several of these oscillatory activities are also altered in the aging process 2 , which makes sleep physiology an attractive target for studying cognitive aging in humans and animal models. The dog has been suggested to be a suitable model for human cognitive aging . Their advantage over rodents in this respect is argued on the basis of a more similar behavioural repertoire 6 and a shared environment 7 . Recently sleep physiology in dogs has received growing attention due to the development of a non-invasive polysomnographic method 8 which opens up a possibility for integrating the study of cognitive aging and sleep in pet dogs. The sleep spindle, which appears as a short (0.5-5 seconds) train of rhythmic and symmetric waves , traceable with EEG and occurring predominantly during non-REM sleep, had been described, but seldom quantified in the dog. Various contradicting accounts about its defining features in canines had been published based on visual inspection alone 8,14-16 , derived from both invasive and non-invasive work. Using criteria for automatic sleep spindle detection previously validated in humans 17 we were able to show that transients in the sigma range (9-16 Hz), characteristic of the human sleep spindle, show a similar association with post-sleep recall of novel information, i.e. dogs with higher learning gain displayed more spindles/minute 18 . The sleep spindle is a particularly attractive target of investigation with regard to aging. Its rate of occurrence (density), amplitude, frequency (waves/second of a single spindle) and duration have each been found to change in humans, from childhood to puberty , from young adult to old age , and between healthy and pathologically aging groups . Age-related changes, in particular those associated with cognitive decline, are characterized by decreased density (spindles/minute) and amplitude . A subset of studies also found an increase in spindle frequency for older subjects 2 , whereas adolescent development is characterized by increased density . A distinction between fast and slow spindles is common in humans . The two sub-types can be topographically distinguished. Fast spindles are predominantly found in central and posterior derivations and oscillate on average ≥13 Hz, whereas slow spindles (≤13 Hz) are predominant in the frontal derivations. The distinction is, however, less clear based on the origin of spindles. Invasive work in cats had originally implied
Tanulmányunkban a 2018 tavaszán készült Fiatal kutatók Magyarországon című felmérés legfőbb eredm... more Tanulmányunkban a 2018 tavaszán készült Fiatal kutatók Magyarországon című felmérés legfőbb eredményeit foglaljuk össze. A tudományos pálya választásában a fiatalok legfőbb motivációját a felfedezés izgalma és a tudományos elhivatottság jelenti. Ez a kezdeti lelkesedés azonban, mely a tevékenység jellegéből természetes módon fakad, és mindenfajta aktív tudománypolitikai stratégia nélkül is megjelenik, önmagában nem elegendő a kutatók hoszszú távú szakmai fejlődéséhez és magánéleti boldogulásához. Kérdőívünk válaszadói számos olyan problémára hívják fel a figyelmet, melyek azonnali kezelést igényelnek. A fiatalok tudományos pályán maradását elsősorban a személyes anyagi nehézségek, a kutatási források hiánya és a nem kiszámítható, nem tervezhető szakmai karrier nehezítik meg, leginkább tehát ezeken a területeken van szükség beavatkozásra ahhoz, hogy a hazai tudományos pálya vonzóvá váljon és az is maradjon a fiatalok számára.
Dominance is well defined in ethology, debated in psychology, and is often unclear among the dog ... more Dominance is well defined in ethology, debated in psychology, and is often unclear among the dog owning public and in the press. However, to date, no study has examined how owners perceive dominance in dogs, and what different behaviours and personality types are used to describe dominant and subordinate individuals. A questionnaire study was launched to investigate the external validity of owner-derived estimates of dominance in dog dyads sharing the same household (N = 1,151). According to the owners, dogs rated as dominant (87%) have priority access to resources (resting place, food, and rewards), undertake certain tasks (defend and lead the group, bark more), display dominance (win fights, lick the other's mouth less, and mark over the other's urine), share certain personality traits (smarter, more aggressive and impulsive), and are older than their partner dog (all p < 0.0001). An age-related hypothesis has been suggested to explain dominance in dogs; but we found that dog age did not explain the occurrence of dominance related behaviours over the owners' estimate of dominance status. Results suggest that owner-derived reports of dominance ranks of dogs living in multi-dog households correspond to ethologically valid behavioural markers of dominance. Size and physical condition were unrelated to the perceived dominance. Surprisingly, in mixed-sex dyads, females were more frequently rated as dominant than males, which might correspond to a higher proportion of neutered females in this subgroup. For future studies that wish to allocate dominance status using owner report, we offer a novel survey.
Aging research has experienced a burst of scientific efforts in the last decades as the growing r... more Aging research has experienced a burst of scientific efforts in the last decades as the growing ratio of elderly people has begun to pose an increased burden on the healthcare and pension systems of developed countries. Although many breakthroughs have been reported in understanding the cellular mechanisms of aging, the intrinsic and extrinsic factors that contribute to senescence on higher biological levels are still barely understood. The dog, Canis familiaris, has already served as a valuable model of human physiology and disease. The possible role the dog could play in aging research is still an open question, although utilization of dogs may hold great promises as they naturally develop age-related cognitive decline, with behavioral and histological characteristics very similar to those of humans. In this regard, family dogs may possess unmatched potentials as models for investigations on the complex interactions between environmental, behavioral, and genetic factors that determine the course of aging. In this review, we summarize the known genetic pathways in aging and their relevance in dogs, putting emphasis on the yet barely described nature of certain aging pathways in canines. Reasons for highlighting the dog as a future aging and gerontology model are also discussed, ranging from its unique evolutionary path shared with humans, its social skills, and the fact that family dogs live together with their owners, and are being exposed to the same environmental effects.
Most common methods that directly show macro-or microscopic anatomy of the brain usually require ... more Most common methods that directly show macro-or microscopic anatomy of the brain usually require the removal of the organ from the neurocranium. However, the brain can be revealed in situ by using proper sectioning techniques. Our aim was to both improve the cryosectioning method, test its limits and create a high-resolution macro-anatomical image series of a Beagle brain, which at the time of the study did not exist. A two-year-old female Beagle has been scanned with CT and MRI ante and post mortem, then the arteries of the head were filled with red resin. After freezing to -80˚C, a neurocranium block was created and was embedded into a water-gelatin mix. Using a special milling device and a DSLR camera, 1112 consecutive RGB-color cryosections were made with a 100 μm layer thickness and captured in high resolution (300 dpi, 24-bit color, and pixel size was 19.5 x 19.5 μm). Image post-processing was done with Adobe Photoshop CS3 and Thermo Scientific Amira 6.0 softwares, and as a result of the proper alignment and coregistration, visualization and comparing was possible with all the applied imaging modalities (CT, MRI, cryosectioning) in any arbitrary plane. Surface models from the arteries, veins, brain and skull were also generated after segmentation in the same coordinate system, giving a unique opportunity for comparing the two-dimensional and three-dimensional anatomy. This is the first study which focuses directly to this high-definition multimodal visualization of the canine brain, and it provides the most accurate results compared to previous cryosectioning studies, as using an improved method, higher image quality, more detailed image, proper color fidelity and lower artefact formation were achieved. Based on the methodology we described, it can serve as a base for future multimodal (CT, MR, augmented-or virtual reality) imaging atlases for medical, educational and scientific purposes.
Dogs living on Bali Island have been free-ranging for thousands of years. A large group of expatr... more Dogs living on Bali Island have been free-ranging for thousands of years. A large group of expatriates sometimes adopt Bali dogs and keep them restricted to their houses and backyards, as is typical in modern western cultures. This provides us with the unique opportunity to compare the personality traits of dogs to their lifestyle either living as human companions or as free-ranging animals, exploring at the same time the impact of demographic variables (such as age, sex, and neutered status) on personality. After controlling for internal consistency of the scales and between-observer variation, we found that free-ranging Bali dogs were rated as less active, less excitable, less aggressive towards animals, and less inclined to chase animals or humans than Bali dogs living as human companions. Among free-ranging dogs, females were found to be more excitable. Females in the whole sample were also more fearful of people. The results of this preliminary study suggest that a change in lifestyle, i.e. being adopted, and living in a confined environment has negative consequences on some canine personality traits, such as activity/excitability, aggression towards animals, and prey drive.
Cognitive aging in dogs has attracted interest due to their utility as an animal model for human ... more Cognitive aging in dogs has attracted interest due to their utility as an animal model for human aging and their need for veterinary care. The latter in particular would benefit substantially from standardized tests for fast and comfortable administration, which would reduce time and financial costs for both owners and practitioners. Here, we examine a battery of tests (the mini mental test, MMT) selected and adapted toward this end in a sample of 20 young (1-5y) and 26 old (10-15y) dogs. Each behavioral test was evaluated for its ability to discriminate between dogs based on their age category. Older dogs displayed less social interest, performed worse in a place-memory test, and seemed both less interested in and less fearful of a novel, moving object, aligning with previous findings and thus confirming the MMT's external validity. The older dogs were also less excitable, assessed by a dog personality questionnaire. Based on these results, for future studies comparing the behavior of young adult and old dogs, we suggest four feasible subtests (greeting, problem box, memory, novel object) that can be conducted outdoors, without complex devices, in a short time (< than 15 min), and evaluated on the spot. To determine which performance levels are within the normal range for old dogs, larger samples grouped by breed and age will need to be tested in future studies.
Background: Although the molecular function of wolframin remains unclear, the lack of this protei... more Background: Although the molecular function of wolframin remains unclear, the lack of this protein is known to cause stress in the endoplasmic reticulum. Some variants in the Wolfram Syndrome 1 gene (WFS1) were associated with various neuropsychiatric disorders in humans, such as aggressiveness, impulsivity and anxiety. Results: Here we present an in silico study predicting a single nucleotide polymorphism (rs852850348) in the canine WFS1 gene which was verified by direct sequencing and was genotyped by a PCR-based technique. We found that the rs852850348 polymorphism is located in a putative microRNA (cfa-miR-8834a and cfa-miR-1838) binding site. Therefore, the molecular effect of allelic variants was studied in a luciferase reporter system that allowed assessing gene expression. We demonstrated that the variant reduced the activity of the reporter protein expression in an allele-specific manner. Additionally, we performed a behavioral experiment and investigated the association with this locus to different performance in this test. Association was found between food possessivity and the studied WFS1 gene polymorphism in the Border collie breed. Conclusions: Based on our findings, the rs852850348 locus might contribute to the genetic risk of possessivity behavior of dogs in at least one breed and might influence the regulation of wolframin expression.
Visual and auditory impairments can have a large impact on performance in cognitive tests. It is ... more Visual and auditory impairments can have a large impact on performance in cognitive tests. It is important to evaluate the sensory capacities of dogs before enrolling them in cognitive tests, in order to exclude sensory impairment as confounding effect. Therefore we designed multiple non-invasive testing paradigms to detect subjects with potential auditory and visual impairment, without requiring extensive training for the dog. Multiple testing was a means to add internal reliability, and to reduce the risk of false positives due to habituation and previous learning or false negatives due to random errors. Our sensory test battery consisted of four subtests: (1) 'Clapping' auditory test, (2) 'Recorded sound' auditory test, (3) 'Distance' visual test, and (4) 'Darkness' visual test. The 'Clapping test' was similar to the clapping test used by veterinarians, with the addition that the clapping was performed at various distances from the dog. In the 'Recorded sound test', the dogs' reaction to various sounds played back at different volumes. In the 'Distance test' we placed a small piece of food on one of four plates placed on the grounds at varying distances from the dogs. In the 'Darkness test', we measured the dogs' performance in walking through an S-shaped route during artificial dusk and daylight-like conditions.
In the Methods section under subheading 'Subjects and Behavioural paradigm' . "15 adult pet dogs,... more In the Methods section under subheading 'Subjects and Behavioural paradigm' . "15 adult pet dogs, mean age ± SD: 3.67 ± 1.91; 8 males, 7 females; from 7 pure breeds (3 Border Collies, 2 Golden Retrievers, 1 Labrador Retriever, 1 Poodle, 1 Belgian Shepherd, 1 Puli, 1 Miniature Schnauzer) and 3 mixed breeds (3 unknown, 1 mixed Briard and 1 mixed Malinois), participated three times in 3-hour-long polysomnography recordings 3 , on a total of 3 days (see Fig. )".
Aging is the largest risk factor in many diseases and mortality alike. As the elderly population ... more Aging is the largest risk factor in many diseases and mortality alike. As the elderly population is expected to increase at an accelerating rate in the future, these phenomena will pose a growing socio-economic burden on societies. To successfully cope with this challenge, a deeper understanding of aging is crucial. In many aspects, the companion dog is an increasingly popular model organism to study aging, with the promise of producing results that are more applicable to humans than the findings that come from the studies of classical model organisms. In this preliminary study we used the whole-genome sequence of two extremely old dogs -age: 22 and 27 years (or 90-135% more, than the average lifespan of dogs) -in order to make the first steps to understand the genetic background of extreme longevity in dogs. We identified more than ∼80 1000 novel SNPs in the two dogs (7500 of which overlapped between them) when compared to three publicly available canine SNP databases, which included SNP information from850 dogs. Most novel mutations (∼52000 SNPs) were identified at non-coding regions, while 4.6% of the remaining SNPs (n∼1600) were at exons, including 670 missense variants -76 of which overlapped between the two animalsacross 472 genes. Based on their gene ontologies, these genes were related -among others -to gene transcription/translation and its regulation, to immune response and the nervous system in general. We also detected 12 loss-of-function mutations, although their actual effect is unclear. Several genetic pathways were also identified, which pathways may be tempting candidates to be investigated in large sample sizes in order to confirm their relevance in extreme longevity in dogs (and possibly, in humans). We hypothesize a possible link between extreme longevity and the regulation of gene transcription/translation, which hypothesis should be further investigated in the future. This phenomenon could define an interesting direction for future research aiming to better understand longevity. The presented preliminary results highlight the utility of the companion dog in the study of the genetic background of longevity and aging.
Several studies on age-related cognitive decline in dogs involve laboratory dogs and prolonged tr... more Several studies on age-related cognitive decline in dogs involve laboratory dogs and prolonged training. We developed two spatial tasks that required a single 1-h session. We tested 107 medium-large sized dogs: Byoung^(N=41, aged 2.5-6.5 years) and Bold^(N=66, aged 8-14.5 years). Our results indicated that, in a discrimination learning task and in a reversal learning task, young dogs learned significantly faster than the old dogs, indicating that these two tasks could successfully be used to investigate differences in spatial learning between young and old dogs. We also provide two novel findings. First, in the reversal learning, the dogs trained based on the location of stimuli learned faster than the dogs trained based on stimulus characteristics. Most old dogs did not learn the task within our cut-off of 50 trials. Training based on an object's location is therefore more appropriate for reversal learning tasks. Second, the contrast between the response to the positive and negative stimuli was narrower in old dogs, compared to young dogs, during the reversal learning task, as well as the cognitive bias test. This measure favors comparability between tasks and between studies. Following the cognitive bias test, we could not find any indication of differences in the positive and negative expectations between young and old dogs. Taken together, these findings do not support the hypothesis that old dogs have more negative expectations than young dogs and the use of the cognitive bias test in older dogs requires further investigation.
To describe the extent of age-related cognitive decline in dogs, information regarding the baseli... more To describe the extent of age-related cognitive decline in dogs, information regarding the baseline occurrence of associated behaviours in the general population is necessary. With a seven-item, data driven Age-Related Changes scale, we evaluated the relationship between sensory functions, training, sex, and the occurrence of behavioural signs associated with cognitive decline across the whole adult lifespan. The twofold difference in lifespan between small and large dogs presents challenges for ageing studies, with no widely accepted method to control for body size as it relates to chronological age and longevity, when comparing behavioural signs of cognitive decline. To address this issue, we utilized relative age, calculated using the estimated expected lifespan of the individuals in our questionnaire study. Signs of cognitive decline were already detectable in' Mature' dogs (at 50-75% of the expected lifespan). Visual, auditory and olfactory impairments all resulted in significantly higher scores on the Age-Related Changes scale. Participating in dog training activities was revealed to be protective against behavioural signs of cognitive decline in aged dogs as perceived by the owners. These results revealed possible beneficial effects of training on cognitive ageing and emphasize the importance of routinely screening the sensory capacities of ageing dogs. (D. Szabó).
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Papers by Eniko Kubinyi