Behaviors associated with sickness (food consumption, weight maintenance, exploratory activity and grooming frequency) were examined on post-surgical days 1, 3, 5, 7 and 9 in male rats treated with progesterone (4. mg/kg) and/or vehicle. Rats with medial frontal cortex contusions showed reduced food consumption on days 1 and 3 (p< 0.01), reduced weight maintenance on days 1, 3, 5, 7 and 9 (p< 0.01), reduced grooming frequency on day 1 (p< .01), and reduced exploratory activity on day 1 (p< 0.01), after injury compared to sham rats. Contusion induced behaviors were not attenuated with 5 days of progesterone treatment (p> 0.05). Progesterone did reduce lesion size at 9 days after injury (p< 0.05). Our results suggest sickness behaviors occur after traumatic brain injury and that they might not respond to some neurosteroidal agents.
Children with an anxious temperament (AT) are at a substantially increased risk to develop anxiety and depression. The young rhesus monkey is ideal for studying the origin of human AT because it shares with humans the genetic, neural, and phenotypic underpinnings of complex social and emotional functioning. Heritability, functional imaging, and gene expression studies of AT in young monkeys revealed that the central nucleus of the amygdala (Ce) is a key environmentally sensitive substrate of this at risk phenotype. Because epigenetic marks (e.g., DNA methylation) can be modulated by environmental stimuli, these data led us to hypothesize a role for DNA methylation in the development of AT. To test this hypothesis, we used reduced representation bisulfite sequencing to examine the cross-sectional genome-wide methylation levels in the Ce of 23 age-matched monkeys (1.3 ± 0.2 years) phenotyped for AT. Because AT reflects a continuous trait-like variable, we used an analytical approach that is consistent with this biology to identify genes in the Ce with methylation patterns that predict AT. Expression data from the Ce of these same monkeys were then used to find differentially methylated candidates linked to altered gene regulation. Two genes particularly relevant to the AT phenotype were BCL11A and JAG1. These transcripts have well-defined roles in neurodevelopmental processes, including neurite arborization and the regulation of neurogenesis. Together, these findings represent a critical step toward understanding the effects of early environment on the neuromolecular mechanisms that underlie the risk to develop anxiety and depressive disorders.
The purpose of the present study was to push the boundaries of cooperation among captive chimpanzees (Pan troglodytes). There has been doubt about the level of cooperation that chimpanzees are able to spontaneously achieve or understand. Would they, without any pre-training or restrictions in partner choice, be able to develop successful joint action? And would they be able to extend cooperation to more than two partners, as they do in nature? Chimpanzees were given a chance to cooperate with multiple partners of their own choosing. All members of the group (N = 11) had simultaneous access to an apparatus that required two (dyadic condition) or three (triadic condition) individuals to pull in a tray baited with food. Without any training, the chimpanzees spontaneously solved the task a total of 3,565 times in both dyadic and triadic combinations. Their success rate and efficiency increased over time, whereas the amount of pulling in the absence of a partner decreased, demonstrating that they had learned the task contingencies. They preferentially approached the apparatus when kin or nonkin of similar rank were present, showing a preference for socially tolerant partners. The forced partner combinations typical of cooperation experiments cannot reveal these abilities, which demonstrate that in the midst of a complex social environment, chimpanzees spontaneously initiate and maintain a high level of cooperative behavior.
by
Thea Hammerschmidt;
Markus P. Kummer;
Dick Terwel;
Ana Martinez;
Ali Gorji;
Hans-Christian Pape;
Karen Rommelfanger;
Jason Schroeder;
Monika Stoll;
Joachim Schultze;
David Weinshenker;
Michael T. Heneka
Background: Degeneration of the locus coeruleus (LC), the major noradrenergic nucleus in the brain, occurs early and is ubiquitous in Alzheimer's disease (AD). Experimental lesions to the LC exacerbate AD-like neuropathology and cognitive deficits in several transgenic mouse models of AD. Because the LC contains multiple neuromodulators known to affect amyloid β toxicity and cognitive function, the specific role of noradrenaline (NA) in AD is not well understood. Methods: To determine the consequences of selective NA deficiency in an AD mouse model, we crossed dopamine β-hydroxylase (DBH) knockout mice with amyloid precursor protein (APP)/presenilin-1 (PS1) mice overexpressing mutant APP and PS1. Dopamine β-hydroxylase (-/-) mice are unable to synthesize NA but otherwise have normal LC neurons and co-transmitters. Spatial memory, hippocampal long-term potentiation, and synaptic protein levels were assessed. Results: The modest impairments in spatial memory and hippocampal long-term potentiation displayed by young APP/PS1 or DBH (-/-) single mutant mice were augmented in DBH (-/-)/APP/PS1 double mutant mice. Deficits were associated with reduced levels of total calcium/calmodulin-dependent protein kinase II and N-methyl-D-aspartate receptor 2A and increased N-methyl-D-aspartate receptor 2B levels and were independent of amyloid β accumulation. Spatial memory performance was partly improved by treatment with the NA precursor drug L-threo-dihydroxyphenylserine. Conclusions: These results indicate that early LC degeneration and subsequent NA deficiency in AD may contribute to cognitive deficits via altered levels of calcium/calmodulin-dependent protein kinase II and N-methyl-D-aspartate receptors and suggest that NA supplementation could be beneficial in early AD.
The field of primate behavior management has had only limited success at preventing and treating abnormal behaviors such as stereotypy and self-injury in captive non-human primates (NHP). In contrast, applied behavior analysts have had great success in treating similar topographies of behavior in human clinical settings. By adapting and adopting the behavioral principles and methodologies commonly used by applied behavior analysts, primatologists may be able to develop more effective ways to analyze, reduce, and prevent these aberrant behaviors in NHP. This paper reviews studies that have used behavior analytic techniques to successfully address problem behaviors in NHP. Additionally, relevant literature from the field of applied behavior analysis is reviewed to illustrate how adopting a theoretical framework that emphasizes the determination of the underlying operant functions of behavior could lead to new behavioral technologies and advance the field of captive primate management.
Relationships between neurodevelopmental functioning and hemodynamic changes in the prefrontal cortex (PFC) were contrasted between children with prenatal alcohol exposure (PAE) and children who differed relative to their history of PAE and the presence of other neurodevelopmental impairment. For all groups, deoxygenated hemoglobin (HBR) levels in the medial PFC area were negatively related to externalizing problems and levels in the medial and right lateral PFC were positively related to errors on a cognitive inhibition task. Hemodynamic changes in the medial and right lateral PFC of children with PAE demonstrated stronger relationships to aspects of executive functioning relative to contrast groups.
Learning to recognize a stimulus category requires experience with its many natural variations. However, the mechanisms that allow a category's sensorineural representation to be updated after experiencing new exemplars are not well understood, particularly at the molecular level. Here we investigate how a natural vocal category induces expression in the auditory system of a key synaptic plasticity effector immediate early gene, Arc/Arg3.1, which is required for memory consolidation. We use the ultrasonic communication system between mouse pups and adult females to study whether prior familiarity with pup vocalizations alters how Arc is engaged in the core auditory cortex after playback of novel exemplars from the pup vocal category. A computerized, 3D surface-assisted cellular compartmental analysis, validated against manual cell counts, demonstrates significant changes in the recruitment of neurons expressing Arc in pup-experienced animals (mothers and virgin females "cocaring" for pups) compared with pup-inexperienced animals (pup-naïve virgins), especially when listening to more familiar, natural calls compared to less familiar but similarly recognized tonal model calls. Our data support the hypothesis that the kinetics of Arc induction to refine cortical representations of sensory categories is sensitive to the familiarity of the sensory experience.
The entorhinal-hippocampal circuit is one of the earliest sites of cortical pathology in Alzheimer's disease (AD). Visuospatial memory paradigms that are mediated by the entorhinal-hippocampal circuit may offer a means to detect memory impairment during the early stages of AD. In this study, we developed a 4-min visuospatial memory paradigm called VisMET (Visuospatial Memory Eye-Tracking Task) that passively assesses memory using eye movements rather than explicit memory judgements. We had 296 control or memory-impaired participants view a set of images followed by a modified version of the images with either an object removed, or a new object added. Healthy controls spent significantly more time viewing these manipulations compared to subjects with mild cognitive impairment and AD. Using a logistic regression model, the amount of time that individuals viewed these manipulations could predict cognitive impairment and disease status with an out of sample area under the receiver-operator characteristic curve of 0.85. Based on these results, VisMET offers a passive, sensitive, and efficient memory paradigm capable of detecting objective memory impairment and predicting cognitive and disease status.
Data from the Oregon Youth Study, consisting of the verbal behavior of 210 adolescent boys determined to be at risk for delinquency (targets) and 210 of their friends (peers), were analyzed for their conformance to the complete family of matching theory equations in light of recent findings from the basic science, and using recently developed analytic techniques. Equations of the classic and modern theories of matching were fitted as ensembles to rates and time allocations of the boys' rule-break and normative talk obtained from conversations between pairs of boys. The verbal behavior of each boy in a conversation was presumed to be reinforced by positive social responses from the other boy. Consistent with recent findings from the basic science, the boys' verbal behavior was accurately described by the modern but not the classic theory of matching. These findings also add support to the assertion that basic principles and processes that are known to govern behavior in laboratory experiments also govern human social behavior in undisturbed natural environments.
Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD), has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta) display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS) is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS). Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological mechanisms underlying social impairments.