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Behavioral perception-action dissociations are widely used to test models of high-level vision, but debates concerning their interpretation have underestimated the role of multisensory mechanisms in such tests. Sensorimotor tasks engage multisensory processing in fundamentally different ways than perceptual tasks, and these differences can modulate dissociations in different ways based on task features. To test this idea, we compared perception and action using a well-understood size-contrast effect, the Uznadze illusion, and manipulated both unimodal and crossmodal stimulation as well as conditions that are known to favor or hinder multisensory integration. Results demonstrated that similar or dissociable effects on perception and action can be observed depending on factors that are known to affect multisensory processing. Specifically, such factors can cause a visual task to be affected by the illusion or remain fully unaffected, whereas a visuomotor task can be affected by the illusion, remain immune from the illusion, or, unexpectedly, even show a clear reverse effect. These findings provide a novel perspective on a long standing debate in behavioral cognitive neuroscience. [ABSTRACT FROM AUTHOR]

There are on-going debates about what is and is not 'mindfulness'. These debates are stifling rigorous academic research as scientific precision is a precursor to shared meaning. While mindfulness is a growing field of research, these divergent and conflated meanings are limiting deeper interdisciplinary research. Interventions designed in one practice context may not be useful in other contexts because meaning is not transferred between settings. This review clarifies the various research domains that study mindfulness and the conceptual and operational definitions in each domain. This two-stage study comprises a scoping review of mindfulness classifications and a comparative content mapping of mindfulness studies from 2015 to 2021. The initial comprehensive search strategy followed the preferred reporting items for scoping reviews and meta-analysis (PRISMA) method. The comparative analysis was conducted using Leximancer. Findings illustrate a complex growing research corpus on mindfulness that is somewhat confused. The results from the scoping review show three shared domains in mindfulness classifications: short-term effects of mindfulness, long-term effects of mindfulness, and mindfulness practices. The results from the content mapping show four domains of mindfulness research: mental health, behavioural change, cognitive neuroscience, and ethical mindfulness. Operational definitions of mindfulness are not articulated clearly in these domains. Conceptual and operational definitions in the 'ethical mindfulness' domain are not yet developed. To enhance scientific progress in mindfulness research, further investigations of mindfulness classifications need to be developed. Content mapping and semantic typology is a potential candidate for future classification. More attention should be paid to developing operational definitions according to specific research domains. Scholars in the ethical mindfulness domain will need solid conceptual and operational definitions to support their research efforts. [ABSTRACT FROM AUTHOR]

Longitudinal and behavioral preclinical animal studies generate complex data, which may not be well matched to statistical approaches common in this literature. Analyses that do not adequately account for complexity may result in overly optimistic study conclusions, with consequences for reproducibility and translational decision-making. Recent work interrogating methodological shortcomings in animal research has not yet comprehensively investigated statistical shortcomings in the analysis of complex longitudinal and behavioral data. To this end, the current cross-sectional meta-research study rigorously reviewed published mouse or rat controlled experiments for motor rehabilitation in three neurologic conditions to evaluate statistical choices and reporting. Medline via PubMed was queried in February 2020 for English-language articles published January 1, 2017- December 31, 2019. Included were articles that used rat or mouse models of stroke, Parkinson's disease, or traumatic brain injury, employed a therapeutic controlled experimental design to determine efficacy, and assessed at least one functional behavioral assessment or global evaluation of function. 241 articles from 99 journals were evaluated independently by a team of nine raters. Articles were assessed for statistical handling of non-independence, animal attrition, outliers, ordinal data, and multiplicity. Exploratory analyses evaluated whether transparency or statistical choices differed as a function of journal factors. A majority of articles failed to account for sources of non-independence in the data (74–93%) and/or did not analytically account for mid-treatment animal attrition (78%). Ordinal variables were often treated as continuous (37%), outliers were predominantly not mentioned (83%), and plots often concealed the distribution of the data (51%) Statistical choices and transparency did not differ with regards to journal rank or reporting requirements. Statistical misapplication can result in invalid experimental findings and inadequate reporting obscures errors. Clinician-scientists evaluating preclinical work for translational promise should be mindful of commonplace errors. Interventions are needed to improve statistical decision-making in preclinical behavioral neurosciences research. [ABSTRACT FROM AUTHOR]

Some claim that recent advances in neuroscience will revolutionize the way we think about human nature and legal culpability. Empirical support for this proposition is mixed. Two highly-cited empirical studies found that irrelevant neuroscientific explanations and neuroimages were highly persuasive to laypersons. However, attempts to replicate these effects have largely been unsuccessful. Two separate experiments tested the hypothesis that neuroscience is susceptible to motivated reasoning, which refers to the tendency to selectively credit or discredit information in a manner that reinforces preexisting beliefs. Participants read a newspaper article about a cutting-edge neuroscience study. Consistent with the hypothesis, participants deemed the hypothetical study sound and the neuroscience persuasive when the outcome of the study was congruent with their prior beliefs, but gave the identical study and neuroscience negative evaluations when it frustrated their beliefs. Neuroscience, it appears, is subject to the same sort of cognitive dynamics as other types of scientific evidence. These findings qualify claims that neuroscience will play a qualitatively different role in the way in which it shapes people's beliefs and informs issues of social policy.

How much can we rely on whether what was reported in a study was actually done? Systematic and independent examination of records, documents and processes through audits are a central element of quality management systems. In the context of current concerns about the robustness and reproducibility of experimental biomedical research audits have been suggested as a remedy a number of times. However, audits are resource intense and time consuming, and due to their very nature may be perceived as inquisition. Consequently, there is very little experience or literature on auditing and assessments in the complex preclinical biomedical research environment. To gain some insight into which audit approaches might best suit biomedical research in academia, in this study we have applied a number of them in a typical academic neuroscience environment consisting of twelve research groups with about 100 researchers, students and technicians, utilizing the full gamut of state-of-the-art methodology. Several types of assessments and internal as well as external audits (including the novel format of a peer audit) were systematically explored by a team of quality management specialists. An experimental design template was developed (and is provided here) that takes into account and mitigates difficulties, risks and systematic errors that may occur during the course of a study. All audits were performed according to a pre-defined workflow developed by us. Outcomes were assessed qualitatively. We asked for feedback from participating employees in every final discussion of an audit and documented this in the audit reports. Based on these reports follow-up audits were improved. We conclude that several realistic options for auditing exist which have the potential to improve preclinical biomedical research in academia, and have listed specific recommendations regarding their benefits and provided practical resources for their implementation (e.g. study design and audit templates, audit workflow). [ABSTRACT FROM AUTHOR]

The survival of an organism depends on the ability to make adaptive decisions to achieve the needs of the organism: where to get food, who to mate with, and how to evade predators. Decision-making is a term used to describe a collection of behavioral and/or computational functions that guide the selection of an option amongst a set of alternatives. Some of these functions may include calculating the costs and benefits of a particular action, evaluating differences in value of each of the alternative outcomes and the likelihood of receiving a particular outcome, using past experiences to generate predictions or expectations about action-outcome associations, and/or integration of past experiences to make novel inferences that can be used in new environments. There is considerable interest in understanding the neurobiological mechanisms that mediate these decision-making functions and recent advances in behavioral approaches, neuroscience techniques, and neuroimaging measures have begun to develop mechanistic links between biology, reward, and decision making. This multidisciplinary work holds great promise for elucidating the biological mechanisms mediating decision-making deficits in normal and abnormal states. The multidisciplinary studies included in this Collection provide new insights into the neuroscience of decision making and reward. [ABSTRACT FROM AUTHOR]

In the field of songbird neuroscience, researchers have used playback of aversive noise bursts to drive changes in song behavior for specific syllables within a bird's song. Typically, a short (~5–10 msec) slice of the syllable is selected for targeting and the average spectrum of the slice is used as a template. Sounds that are sufficiently close to the template are considered a match. If other syllables have portions that are spectrally similar to the target, false positive errors will weaken the operant contingency. We present a gradient descent method for template optimization that increases the separation in distance between target and distractors slices, greatly improving targeting accuracy. Applied to songs from five adult Bengalese finches, the fractional reduction in errors for sub-syllabic slices was 51.54±22.92%. At the level of song syllables, we use an error metric that controls for the vastly greater number of distractors vs. target syllables. Setting 5% average error (misses + false positives) as a minimal performance criterion, the number of targetable syllables increased from 3 to 16 out of 61 syllables. At 10% error, targetable syllables increased from 11 to 26. By using simple and robust linear discriminant methods, the algorithm reaches near asymptotic performance when using 10 songs as training data, and the error increases by <2.3% on average when using only a single song for training. Targeting is temporally precise, with average jitter of 3.33 msec for the 16 accurately targeted syllables. Because the algorithm is concerned only with the problem of template selection, it can be used as a simple and robust front end for existing hardware and software implementations for triggered feedback. [ABSTRACT FROM AUTHOR]

Recent technical advancements in neural engineering allow for precise recording and control of neural circuits simultaneously, opening up new opportunities for closed-loop neural control. In this work, a rapid spike sorting system was developed based on template matching to rapidly calculate instantaneous firing rates for each neuron in a multi-unit extracellular recording setting. Cluster templates were first generated by a desktop computer using a non-parameter spike sorting algorithm (Super-paramagnetic clustering) and then transferred to a field-programmable gate array digital circuit for rapid sorting through template matching. Two different matching techniques–Euclidean distance (ED) and correlational matching (CM)–were compared for the accuracy of sorting and the performance of calculating firing rates. The performance of the system was first verified using publicly available artificial data and was further confirmed with pre-recorded neural spikes from an anesthetized Mongolian gerbil. Real-time recording and sorting from an awake mouse were also conducted to confirm the system performance in a typical behavioral neuroscience experimental setting. Experimental results indicated that high sorting accuracies were achieved for both template-matching methods, but CM can better handle spikes with non-Gaussian spike distributions, making it more robust for in vivo recording. The technique was also compared to several other off-line spike sorting algorithms and the results indicated that the sorting accuracy is comparable but sorting time is significantly shorter than these other techniques. A low sorting latency of under 2 ms and a maximum spike sorting rate of 941 spikes/second have been achieved with our hybrid hardware/software system. The low sorting latency and fast sorting rate allow future system developments of neural circuit modulation through analyzing neural activities in real-time. [ABSTRACT FROM AUTHOR]

Operant conditioning is a crucial tool in neuroscience research for probing brain function. While molecular, anatomical and even physiological techniques have seen radical increases in throughput, efficiency, and reproducibility in recent years, behavioural tools have somewhat lagged behind. Here we present a fully automated, high-throughput system for self-initiated conditioning of up to 25 group-housed, radio-frequency identification (RFID) tagged mice over periods of several months and >106 trials. We validate this “AutonoMouse” system in a series of olfactory behavioural tasks and show that acquired data is comparable to previous semi-manual approaches. Furthermore, we use AutonoMouse to systematically probe the impact of graded olfactory bulb lesions on olfactory behaviour, demonstrating that while odour discrimination in general is robust to even most extensive disruptions, small olfactory bulb lesions already impair odour detection. Discrimination learning of similar mixtures as well as learning speed are in turn reliably impacted by medium lesion sizes. The modular nature and open-source design of AutonoMouse should allow for similar robust and systematic assessments across neuroscience research areas. [ABSTRACT FROM AUTHOR]

Many contemporary neuroscience experiments utilize high-throughput approaches to simultaneously collect behavioural data from many animals. The resulting data are often complex in structure and are subjected to systematic biases, which require new approaches for analysis and normalization. This study addressed the normalization need by establishing an approach based on linear-regression modeling. The model was established using a dataset of visual motor response (VMR) obtained from several strains of wild-type (WT) zebrafish collected at multiple stages of development. The VMR is a locomotor response triggered by drastic light change, and is commonly measured repeatedly from multiple larvae arrayed in 96-well plates. This assay is subjected to several systematic variations. For example, the light emitted by the machine varies slightly from well to well. In addition to the light-intensity variation, biological replication also created batch-batch variation. These systematic variations may result in differences in the VMR and must be normalized. Our normalization approach explicitly modeled the effect of these systematic variations on VMR. It also normalized the activity profiles of different conditions to a common baseline. Our approach is versatile, as it can incorporate different normalization needs as separate factors. The versatility was demonstrated by an integrated normalization of three factors: light-intensity variation, batch-batch variation and baseline. After normalization, new biological insights were revealed from the data. For example, we found larvae of TL strain at 6 days post-fertilization (dpf) responded to light onset much stronger than the 9-dpf larvae, whereas previous analysis without normalization shows that their responses were relatively comparable. By removing systematic variations, our model-based normalization can facilitate downstream statistical comparisons and aid detecting true biological differences in high-throughput studies of neurobehaviour. [ABSTRACT FROM AUTHOR]

Legal theorists have characterized physical evidence of brain dysfunction as a double-edged sword, wherein the very quality that reduces the defendant’s responsibility for his transgression could simultaneously increase motivations to punish him by virtue of his apparently increased dangerousness. However, empirical evidence of this pattern has been elusive, perhaps owing to a heavy reliance on singular measures that fail to distinguish between plural, often competing internal motivations for punishment. The present study employed a test of the theorized double-edge pattern using a novel approach designed to separate such motivations. We asked a large sample of participants (N = 330) to render criminal sentencing judgments under varying conditions of the defendant’s mental health status (Healthy, Neurobiological Disorder, Psychological Disorder) and the disorder’s treatability (Treatable, Untreatable). As predicted, neurobiological evidence simultaneously elicited shorter prison sentences (i.e., mitigating) and longer terms of involuntary hospitalization (i.e., aggravating) than equivalent psychological evidence. However, these effects were not well explained by motivations to restore treatable defendants to health or to protect society from dangerous persons but instead by deontological motivations pertaining to the defendant’s level of deservingness and possible obligation to provide medical care. This is the first study of its kind to quantitatively demonstrate the paradoxical effect of neuroscientific trial evidence and raises implications for how such evidence is presented and evaluated. [ABSTRACT FROM AUTHOR]

If a doctoral dissertation represents an original investigation that makes a contribution to one’s field, then dissertation research could, and arguably should, be disseminated into the scientific literature. However, the extent and nature of dissertation publication remains largely unknown within psychology. The present study investigated the peer-reviewed publication outcomes of psychology dissertation research in the United States. Additionally, we examined publication lag, scientific impact, and variations across subfields. To investigate these questions, we first drew a stratified random cohort sample of 910 psychology Ph.D. dissertations from ProQuest Dissertations & Theses. Next, we conducted comprehensive literature searches for peer-reviewed journal articles derived from these dissertations published 0–7 years thereafter. Published dissertation articles were coded for their bibliographic details, citation rates, and journal impact metrics. Results showed that only one-quarter (25.6% [95% CI: 23.0, 28.4]) of dissertations were ultimately published in peer-reviewed journals, with significant variations across subfields (range: 10.1 to 59.4%). Rates of dissertation publication were lower in professional/applied subfields (e.g., clinical, counseling) compared to research/academic subfields (e.g., experimental, cognitive). When dissertations were published, however, they often appeared in influential journals (e.g., Thomson Reuters Impact Factor M = 2.84 [2.45, 3.23], 5-year Impact Factor M = 3.49 [3.07, 3.90]) and were cited numerous times (Web of Science citations per year M = 3.65 [2.88, 4.42]). Publication typically occurred within 2–3 years after the dissertation year. Overall, these results indicate that the large majority of Ph.D. dissertation research in psychology does not get disseminated into the peer-reviewed literature. The non-publication of dissertation research appears to be a systemic problem affecting both research and training in psychology. Efforts to improve the quality and “publishability” of doctoral dissertation research could benefit psychological science on multiple fronts. [ABSTRACT FROM AUTHOR]

Measuring temporal discounting through the use of intertemporal choice tasks is now the gold standard method for quantifying human choice impulsivity (impatience) in neuroscience, psychology, behavioral economics, public health and computational psychiatry. A recent area of growing interest is individual differences in discounting levels, as these may predispose to (or protect from) mental health disorders, addictive behaviors, and other diseases. At the same time, more and more studies have been dedicated to the quantification of individual attitudes towards risk, which have been measured in many clinical and non-clinical populations using closely related techniques. Economists have pointed to interactions between measurements of time preferences and risk preferences that may distort estimations of the discount rate. However, although becoming standard practice in economics, discount rates and risk preferences are rarely measured simultaneously in the same subjects in other fields, and the magnitude of the imposed distortion is unknown in the assessment of individual differences. Here, we show that standard models of temporal discounting —such as a hyperbolic discounting model widely present in the literature which fails to account for risk attitudes in the estimation of discount rates— result in a large and systematic pattern of bias in estimated discounting parameters. This can lead to the spurious attribution of differences in impulsivity between individuals when in fact differences in risk attitudes account for observed behavioral differences. We advance a model which, when applied to standard choice tasks typically used in psychology and neuroscience, provides both a better fit to the data and successfully de-correlates risk and impulsivity parameters. This results in measures that are more accurate and thus of greater utility to the many fields interested in individual differences in impulsivity. [ABSTRACT FROM AUTHOR]

Macaques are often motivated to perform in neuroscientific experiments by implementing fluid restriction protocols. Daily access to water is controlled and the monkeys are rewarded with droplets of fluid for performing correct trials in the laboratory. Although these protocols are widely used and highly effective, it is important from a 3Rs perspective to investigate refinements that may help to lessen the severity of the fluid restriction applied. We assessed the use of social stimuli (images of conspecifics) as rewards for four rhesus macaques performing simple cognitive tasks. We found that individual preferences for images of male faces, female perinea and control stimuli could be identified in each monkey. However, using preferred images did not translate into effective motivators on a trial-by-trial basis: animals preferred fluid rewards, even when fluid restriction was relaxed. There was no difference in the monkeys’ performance of a task when using greyscale versus colour images. Based on our findings, we cannot recommend the use of social stimuli, in this form, as a refinement to current fluid restriction protocols. We discuss the potential alternatives and possibilities for future research. [ABSTRACT FROM AUTHOR]

The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ) diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases. [ABSTRACT FROM AUTHOR]

We designed a behavioural paradigm for vibro-tactile detection to characterise the sampling time and performance in the rat whisker sensory system. Rats initiated a trial by nose-poking into an aperture where their whiskers came into contact with two meshes. A continuous nose-poke for a random duration triggered stimulus presentation. Stimuli were a sequence of discrete Gaussian deflections of the mesh that increased in amplitude over time – across 5 conditions, time to maximum amplitude varied from 0.5 to 8 seconds. Rats indicated the detected stimulus by choosing between two reward spouts. Two rats completed more than 500 trials per condition. Rats' stimulus sampling duration increased and performance dropped with increasing task difficulty. For all conditions the median reaction time was longer for correct trials than incorrect trials. Higher rates of increment in stimulus amplitude resulted in faster rise in performance as a function of stimulus sampling duration. Rats' behaviour indicated a dynamic stimulus sampling whereby nose-poke was maintained until a stimulus was correctly identified or the rat experienced a false alarm. The perception was then manifested in behaviour after a motor delay. We thus modelled the results with 3 parameters: signal detection, false alarm, and motor delay. The model captured the main features of the data and produced parameter estimates that were biologically plausible and highly similar across the two rats. [ABSTRACT FROM AUTHOR]

Expanding interest in oxytocin, particularly the role of endogenous oxytocin in human social behavior, has created a pressing need for replication of results and verification of assay methods. In this study, we sought to replicate and extend previous results correlating plasma oxytocin with trust and trustworthy behavior. As a necessary first step, the two most commonly used commercial assays were compared in human plasma via the addition of a known quantity of exogenous oxytocin, with and without sample extraction. Plasma sample extraction was found to be critical in obtaining repeatable concentrations of oxytocin. In the subsequent trust experiment, twelve samples in duplicate, from each of 82 participants, were collected over approximately six hours during the performance of a Prisoner’s Dilemma task paradigm that stressed human interpersonal trust. We found no significant relationship between plasma oxytocin concentrations and trusting or trustworthy behavior. In light of these findings, previous published work that used oxytocin immunoassays without sample extraction should be reexamined and future research exploring links between endogenous human oxytocin and trust or social behavior should proceed with careful consideration of methods and appropriate biofluids for analysis. [ABSTRACT FROM AUTHOR]

Introduction: During social interactions, our own physiological responses influence those of others. Synchronization of physiological (and behavioural) responses can facilitate emotional understanding and group coherence through inter-subjectivity. Here we investigate if observing cues indicating a change in another's body temperature results in a corresponding temperature change in the observer. Methods: Thirty-six healthy participants (age; 22.9±3.1 yrs) each observed, then rated, eight purpose-made videos (3 min duration) that depicted actors with either their right or left hand in visibly warm (warm videos) or cold water (cold videos). Four control videos with the actors' hand in front of the water were also shown. Temperature of participant observers' right and left hands was concurrently measured using a thermistor within a Wheatstone bridge with a theoretical temperature sensitivity of <0.0001°C. Temperature data were analysed in a repeated measures ANOVA (temperature × actor's hand × observer's hand). Results: Participants rated the videos showing hands immersed in cold water as being significantly cooler than hands immersed in warm water, F(1,34) = 256.67, p<0.001. Participants' own hands also showed a significant temperature-dependent effect: hands were significantly colder when observing cold vs. warm videos F(1,34) = 13.83, p = 0.001 with post-hoc t-test demonstrating a significant reduction in participants' own left (t(35) = −3.54, p = 0.001) and right (t(35) = −2.33, p = 0.026) hand temperature during observation of cold videos but no change to warm videos (p>0.1). There was however no evidence of left-right mirroring of these temperature effects p>0.1). Sensitivity to temperature contagion was also predicted by inter-individual differences in self-report empathy. Conclusions: We illustrate physiological contagion of temperature in healthy individuals, suggesting that empathetic understanding for primary low-level physiological challenges (as well as more complex emotions) are grounded in somatic simulation. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans is a useful model to study the neuronal or molecular basis for behavioral choice, a specific form of decision-making. Although it has been implied that both D1-like and D2-like dopamine receptors may contribute to the control of decision-making in mammals, the genetic interactions between D1-like and D2-like dopamine receptors in regulating decision-making are still largely unclear. In the present study, we investigated the molecular control of behavioral choice between conflicting alternatives (diacetyl and Cu2+) by D1-like and D2-like dopamine receptors and their possible genetic interactions with C. elegans as the assay system. In the behavioral choice assay system, mutation of dop-1 gene encoding D1-like dopamine receptor resulted in the enhanced tendency to cross the Cu2+ barrier compared with wild-type. In contrast, mutations of dop-2 or dop-3 gene encoding D2-like dopamine receptor caused the weak tendency to cross the Cu2+ barrier compared with wild-type. During the control of behavioral choice, DOP-3 antagonistically regulated the function of DOP-1. The behavioral choice phenotype of dop-2; dop-1dop-3 triple mutant further confirmed the possible antagonistic function of D2-like dopamine receptor on D1-like dopamine receptor in regulating behavioral choice. The genetic assays further demonstrate that DOP-3 might act through Gαo signaling pathway encoded by GOA-1 and EGL-10, and DOP-1 might act through Gαq signaling pathway encoded by EGL-30 and EAT-16 to regulate the behavioral choice. DOP-1 might function in cholinergic neurons to regulate the behavioral choice, whereas DOP-3 might function in GABAergic neurons, RIC, and SIA neurons to regulate the behavioral choice. In this study, we provide the genetic evidence to indicate the antagonistic relationship between D1-like dopamine receptor and D2-like dopamine receptor in regulating the decision-making of animals. Our data will be useful for understanding the complex functions of dopamine receptors in regulating decision-making in animals. [ABSTRACT FROM AUTHOR]

Many animal species engage in various forms of solitary object play, but this activity seems to be of particular importance in primates. If playing objects constitute a valuable resource, and access to such objects is limited, a competitive context may arise. We inserted a unique toy within a mini-colony of long-tailed macaque (Macaca fascicularis) and compared their behaviors to sessions without playing object. An automatic color-based 3D video device was used to track the positions of each animal and the toy, and this data was categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). As expected, the delay to first access to the object reflected the hierarchy of the colony, indicating that a competition took place to own this unique resource of entertainment. In addition, we found that the amount of object play was not correlated with social or foraging behavior, suggesting independent motivational mechanisms. Conversely, object playing time was negatively correlated with idling time, thus indicating its relation to pastime activities. Interestingly, the amount of social contacts in the group was significantly reduced by the heightened competitive context, suggesting that competitors are more likely to be perceived as potential threat requiring caution, as shown in humans. Experimental manipulation of competitive contexts in primates reveals common mental processes involved in social judgment, and shows that access to valuable resources can be a sufficient cause for variations in group cohesion. [ABSTRACT FROM AUTHOR]

Objective: Because reduction of the microtubule-associated protein Tau has beneficial effects in mouse models of Alzheimer's disease and epilepsy, we wanted to determine whether this strategy can also improve the outcome of mild traumatic brain injury (TBI). Methods: We adapted a mild frontal impact model of TBI for wildtype C57Bl/6J mice and characterized the behavioral deficits it causes in these animals. The Barnes maze, Y maze, contextual and cued fear conditioning, elevated plus maze, open field, balance beam, and forced swim test were used to assess different behavioral functions. Magnetic resonance imaging (MRI, 7 Tesla) and histological analysis of brain sections were used to look for neuropathological alterations. We also compared the functional effects of this TBI model and of controlled cortical impact in mice with two, one or no Tau alleles. Results: Repeated (2-hit), but not single (1-hit), mild frontal impact impaired spatial learning and memory in wildtype mice as determined by testing of mice in the Barnes maze one month after the injury. Locomotor activity, anxiety, depression and fear related behaviors did not differ between injured and sham-injured mice. MRI imaging did not reveal focal injury or mass lesions shortly after the injury. Complete ablation or partial reduction of tau prevented deficits in spatial learning and memory after repeated mild frontal impact. Complete tau ablation also showed a trend towards protection after a single controlled cortical impact. Complete or partial reduction of tau also reduced the level of axonopathy in the corpus callosum after repeated mild frontal impact. Interpretation: Tau promotes or enables the development of learning and memory deficits and of axonopathy after mild TBI, and tau reduction counteracts these adverse effects. [ABSTRACT FROM AUTHOR]

Speech impairment is one of the most intriguing and least understood effects of alcohol on cognitive function, largely due to the lack of data on alcohol effects on vocalizations in the context of an appropriate experimental model organism. Zebra finches, a representative songbird and a premier model for understanding the neurobiology of vocal production and learning, learn song in a manner analogous to how humans learn speech. Here we show that when allowed access, finches readily drink alcohol, increase their blood ethanol concentrations (BEC) significantly, and sing a song with altered acoustic structure. The most pronounced effects were decreased amplitude and increased entropy, the latter likely reflecting a disruption in the birds’ ability to maintain the spectral structure of song under alcohol. Furthermore, specific syllables, which have distinct acoustic structures, were differentially influenced by alcohol, likely reflecting a diversity in the neural mechanisms required for their production. Remarkably, these effects on vocalizations occurred without overt effects on general behavioral measures, and importantly, they occurred within a range of BEC that can be considered risky for humans. Our results suggest that the variable effects of alcohol on finch song reflect differential alcohol sensitivity of the brain circuitry elements that control different aspects of song production. They also point to finches as an informative model for understanding how alcohol affects the neuronal circuits that control the production of learned motor behaviors. [ABSTRACT FROM AUTHOR]

The 5-choice serial reaction time task (5CSRTT) has been widely used to study attention and impulse control in rodents. In order to mimic cognitive impairments in psychiatry, one approach has been to use acute administration of NMDA antagonists. This disruption in glutamatergic transmission leads to impairments in accuracy, omissions, and premature responses although findings have been inconsistent. In this study, we further investigated glutamatergic mechanisms using a novel version of the 5CSRTT, which we have previously shown to be more sensitive to cognitive enhancers. We first investigated the effects of systemic treatment with NMDA antagonists. We also carried out a preliminary investigation using targeted medial prefrontal cortex infusions of a NMDA antagonist (MK801), mGluR2/3 antagonist (LY341495), and mGluR7 negative allosteric modulator (MMPIP). Acute systemic administration of the different NMDA antagonists had no specific effects on accuracy. At higher doses PCP, ketamine, and memantine, increased omissions and affected other measures suggesting a general disruption in task performance. Only MK801 increased premature responses, and reduced omissions at lower doses suggesting stimulant like effects. None of the NMDA antagonists affected accuracy or any other measures when tested using a short stimulus challenge. Infusions of MK801 had no effect on accuracy but increased premature responses following infralimbic, but not prelimbic infusion. LY341495 had no effects in either brain region but a decrease in accuracy was observed following prelimbic infusion of MMPIP. Contrary to our hypothesis, disruptions to glutamate transmission using NMDA antagonists did not induce any clear deficits in accuracy in this modified version of the 5CSRTT. We also found that the profile of effects for MK801 differed from those observed with PCP, ketamine, and memantine. The effects of MK801 in the infralimbic cortex add to the literature indicating this brain region and glutamate play an important role in impulse control. [ABSTRACT FROM AUTHOR]

The smoking of tobacco continues to be the leading cause of premature death worldwide and is linked to the development of a number of serious illnesses including heart disease, respiratory diseases, stroke and cancer. Currently, cell line based toxicity assays are typically used to gain information on the general toxicity of cigarettes and other tobacco products. However, they provide little information regarding the complex disease-related changes that have been linked to smoking. The ethical concerns and high cost associated with mammalian studies have limited their widespread use for in vivo toxicological studies of tobacco. The zebrafish has emerged as a low-cost, high-throughput, in vivo model in the study of toxicology. In this study, smoke condensates from 2 reference cigarettes and 6 Canadian brands of cigarettes with different design features were assessed for acute, developmental, cardiac, and behavioural toxicity (neurotoxicity) in zebrafish larvae. By making use of this multifaceted approach we have developed an in vivo model with which to compare the toxicity profiles of smoke condensates from cigarettes with different design features. This model system may provide insights into the development of smoking related disease and could provide a cost-effective, high-throughput platform for the future evaluation of tobacco products. [ABSTRACT FROM AUTHOR]

Birdsong consists of species-specific learned vocal sequences that are used primarily to attract mates and to repel competitors during the breeding season. However, many birds continue to sing at times when vocal production has no immediate or obvious impact on conspecific behavior. The mechanisms that ensure that animals produce important behaviors in contexts in which the function of these behaviors is not immediate or obvious are not known. One possibility is that animals engage in such behaviors because they are associated with pleasure. Here we examined the hypothesis that male European starlings sing outside of the breeding season in part because the act of singing in this context is facilitated and/or maintained by opioid-mediated reward. We measured song-associated reward using a conditioned place preference (CPP) test in male starlings producing fall, non-breeding season-typical song. We used quantitative real time PCR to measure expression of the enkephalin opioid precursor preproenkephalin (PENK) and mu opioid receptors (MOR) in the medial preoptic nucleus (POM; a region in which opioids are implicated in both reward and starling fall song) and additionally the song control region HVC as a control. Starlings developed a strong preference for a place that had been paired previously with the act of producing fall-typical song, indicating that fall song production was associated with a positive affective state. Both PENK and MOR mRNA expression in the POM, but not HVC, correlated positively with both individual reward state (as reflected in CPP) and undirected singing behavior. These results suggest that singing induces opioid receptor and enkephalin expression in the POM and consequent reward, and/or that opioid release in the POM induced by individual or environmental factors (e.g., the presence of food, safety of a flock or the absence of predators) induces a positive affective state which then facilitates singing behavior. [ABSTRACT FROM AUTHOR]

We investigated performance-derived measures of executive control, and their relationship with self- and informant reported executive functions in everyday life, in treatment-naive adults with newly diagnosed Attention Deficit Hyperactivity Disorder (ADHD; n = 36) and in healthy controls (n = 35). Sustained attentional control and response inhibition were examined with the Test of Variables of Attention (T.O.V.A.). Delayed responses, increased reaction time variability, and higher omission error rate to Go signals in ADHD patients relative to controls indicated fluctuating levels of attention in the patients. Furthermore, an increment in NoGo commission errors when Go stimuli increased relative to NoGo stimuli suggests reduced inhibition of task-irrelevant stimuli in conditions demanding frequent responding. The ADHD group reported significantly more cognitive and behavioral executive problems than the control group on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). There were overall not strong associations between task performance and ratings of everyday executive function. However, for the ADHD group, T.O.V.A. omission errors predicted self-reported difficulties on the Organization of Materials scale, and commission errors predicted informant reported difficulties on the same scale. Although ADHD patients endorsed more symptoms of depression and anxiety on the Achenbach System of Empirically Based Assessment (ASEBA) than controls, ASEBA scores were not significantly associated with T.O.V.A. performance scores. Altogether, the results indicate multifaceted alteration of attentional control in adult ADHD, and accompanying subjective difficulties with several aspects of executive function in everyday living. The relationships between the two sets of data were modest, indicating that the measures represent non-redundant features of adult ADHD. [ABSTRACT FROM AUTHOR]

Human observers are able to perceive the motion direction of actions (either forward or backward) on the basis of the articulatory, relative motion of the limbs, even when the actions are shown under point-light conditions. However, most studies have focused on the action of walking. The primary purpose of the present study is to further investigate the perception of articulatory motion in different point-light actions (walking, crawling, hand walking, and rowing). On each trial, participants were presented with a forward or backward moving person and they had to decide on the direction of articulatory motion of the person. We analyzed sensitivity (d') as well as response bias (c). In addition to the type of action, the diagnosticity of the available information was manipulated by varying the visibility of the body parts (full body, only upper limbs, or only lower limbs) and the viewpoint from which the action was seen (from frontal view to sagittal view). We observe that, depending on the specific action, perception of direction of motion is driven by different body parts. Implications for the possible existence of a life detector, i.e., an evolutionarily old and innate visual filter that is tuned to quickly and automatically detect the presence of a moving living organism and direct attention to it, are discussed. [ABSTRACT FROM AUTHOR]

Knockout (KO) mice that lack the dopamine transporter (SL6A3; DAT) display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD) and that these drugs may act upon serotonin (5-HT) systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA) systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics. [ABSTRACT FROM AUTHOR]

During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive. [ABSTRACT FROM AUTHOR]

Planarians are free-living aquatic flatworms that possess a well-documented photophobic response to light. With a true central nervous system and simple cerebral eyes (ocelli), planarians are an emerging model for regenerative eye research. However, comparatively little is known about the physiology of their photoreception or how their behavior is affected by various wavelengths. Most phototactic studies have examined planarian behavior using white light. Here, we describe a novel planarian behavioral assay to test responses to small ranges of visible wavelengths (red, blue, green), as well as ultraviolet (UV) and infrared (IR) which have not previously been examined. Our data show that planarians display behavioral responses across a range of wavelengths. These responses occur in a hierarchy, with the shortest wavelengths (UV) causing the most intense photophobic responses while longer wavelengths produce no effect (red) or an apparent attraction (IR). In addition, our data reveals that planarian photophobia is comprised of both a general photophobic response (that drives planarians to escape the light source regardless of wavelength) and wavelength-specific responses that encompass specific behavioral reactions to individual wavelengths. Our results serve to improve the understanding of planarian phototaxis and suggest that behavioral studies performed with white light mask a complex behavioral interaction with the environment. [ABSTRACT FROM AUTHOR]

Neuroprosthesis research aims to enable communication between the brain and external assistive devices while restoring lost functionality such as occurs from stroke, spinal cord injury or neurodegenerative diseases. In future closed-loop sensorimotor prostheses, one approach is to use neuromodulation as direct stimulus to the brain to compensate for a lost sensory function and help the brain to integrate relevant information for commanding external devices via, e.g. movement intention. Current neuromodulation techniques rely mainly of electrical stimulation. Here we focus specifically on the question of eliciting a biomimetically relevant sense of touch by direct stimulus of the somatosensory cortex by introducing optogenetic techniques as an alternative to electrical stimulation. We demonstrate that light activated opsins can be introduced to target neurons in the somatosensory cortex of non-human primates and be optically activated to create a reliably detected sensation which the animal learns to interpret as a tactile sensation localized within the hand. The accomplishment highlighted here shows how optical stimulation of a relatively small group of mostly excitatory somatosensory neurons in the nonhuman primate brain is sufficient for eliciting a useful sensation from data acquired by simultaneous electrophysiology and from behavioral metrics. In this first report to date on optically neuromodulated behavior in the somatosensory cortex of nonhuman primates we do not yet dissect the details of the sensation the animals exerience or contrast it to those evoked by electrical stimulation, issues of considerable future interest. [ABSTRACT FROM AUTHOR]

Genetic alterations or pharmacological treatments affecting endocannabinoid signaling have profound effects on synaptic and neuronal properties and, under certain conditions, may improve higher brain functions. Down syndrome (DS), a developmental disorder caused by triplication of chromosome 21, is characterized by deficient cognition and inevitable development of the Alzheimer disease (AD) type pathology during aging. Here we used JZL184, a selective inhibitor of monoacylglycerol lipase (MAGL), to examine the effects of chronic MAGL inhibition on the behavioral, biochemical, and synaptic properties of aged Ts65Dn mice, a genetic model of DS. In both Ts65Dn mice and their normosomic (2N) controls, JZL184-treatment increased brain levels of 2-arachidonoylglycerol (2-AG) and decreased levels of its metabolites such as arachidonic acid, prostaglandins PGD2, PGE2, PGFα, and PGJ2. Enhanced spontaneous locomotor activity of Ts65Dn mice was reduced by the JZL184-treatement to the levels observed in 2N animals. Deficient long-term memory was also improved, while short-term and working types of memory were unaffected. Furthermore, reduced hippocampal long-term potentiation (LTP) was increased in the JZL184-treated Ts65Dn mice to the levels observed in 2N mice. Interestingly, changes in synaptic plasticity and behavior were not observed in the JZL184-treated 2N mice suggesting that the treatment specifically attenuated the defects in the trisomic animals. The JZL184-treatment also reduced the levels of Aβ40 and Aβ42, but had no effect on the levels of full length APP and BACE1 in both Ts65Dn and 2N mice. These data show that chronic MAGL inhibition improves the behavior and brain functions in a DS model suggesting that pharmacological targeting of MAGL may be considered as a perspective new approach for improving cognition in DS. [ABSTRACT FROM AUTHOR]

Repeated noxious stimulation produces long-term sensitization of defensive withdrawal reflexes in Aplysia californica, a form of long-term memory that requires changes in both transcription and translation. Previous work has identified 10 transcripts which are rapidly up-regulated after long-term sensitization training in the pleural ganglia. Here we use quantitative PCR to begin examining how these transcriptional changes are expressed in different CNS loci related to defensive withdrawal reflexes at 1 and 24 hours after long-term sensitization training. Specifically, we sample from a) the sensory wedge of the pleural ganglia, which exclusively contains the VC nociceptor cell bodies that help mediate input to defensive withdrawal circuits, b) the remaining pleural ganglia, which contain withdrawal interneurons, and c) the pedal ganglia, which contain many motor neurons. Results from the VC cluster show different temporal patterns of regulation: 1) rapid but transient up-regulation of Aplysia homologs of C/EBP, C/EBPγ, and CREB1, 2) delayed but sustained up-regulation of BiP, Tolloid/BMP-1, and sensorin, 3) rapid and sustained up-regulation of Egr, GlyT2, VPS36, and an uncharacterized protein (LOC101862095), and 4) an unexpected lack of regulation of Aplysia homologs of calmodulin (CaM) and reductase-related protein (RRP). Changes in the remaining pleural ganglia mirror those found in the VC cluster at 1 hour but with an attenuated level of regulation. Because these samples had almost no expression of the VC-specific transcript sensorin, our data suggests that sensitization training likely induces transcriptional changes in either defensive withdrawal interneurons or neurons unrelated to defensive withdrawal. In the pedal ganglia, we observed only a rapid but transient increase in Egr expression, indicating that long-term sensitization training is likely to induce transcriptional changes in motor neurons but raising the possibility of different transcriptional endpoints in this cell type. [ABSTRACT FROM AUTHOR]

Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. [ABSTRACT FROM AUTHOR]

There is growing evidence from both behavioral and neurophysiological approaches that primates are able to rapidly discriminate visually between snakes and innocuous stimuli. Recent behavioral evidence suggests that primates are also able to discriminate the level of threat posed by snakes, by responding more intensely to a snake model poised to strike than to snake models in coiled or sinusoidal postures (Etting and Isbell 2014). In the present study, we examine the potential for an underlying neurological basis for this ability. Previous research indicated that the pulvinar is highly sensitive to snake images. We thus recorded pulvinar neurons in Japanese macaques (Macaca fuscata) while they viewed photos of snakes in striking and non-striking postures in a delayed non-matching to sample (DNMS) task. Of 821 neurons recorded, 78 visually responsive neurons were tested with the all snake images. We found that pulvinar neurons in the medial and dorsolateral pulvinar responded more strongly to snakes in threat displays poised to strike than snakes in non-threat-displaying postures with no significant difference in response latencies. A multidimensional scaling analysis of the 78 visually responsive neurons indicated that threat-displaying and non-threat-displaying snakes were separated into two different clusters in the first epoch of 50 ms after stimulus onset, suggesting bottom-up visual information processing. These results indicate that pulvinar neurons in primates discriminate between poised to strike from those in non-threat-displaying postures. This neuronal ability likely facilitates behavioral discrimination and has clear adaptive value. Our results are thus consistent with the Snake Detection Theory, which posits that snakes were instrumental in the evolution of primate visual systems. [ABSTRACT FROM AUTHOR]

A brand name can be considered a mental category. Similarity-based categorization theory has been used to explain how consumers judge a new product as a member of a known brand, a process called brand extension evaluation. This study was an event-related potential study conducted in two experiments. The study found a two-stage categorization process reflected by the P2 and N400 components in brand extension evaluation. In experiment 1, a prime–probe paradigm was presented in a pair consisting of a brand name and a product name in three conditions, i.e., in-category extension, similar-category extension, and out-of-category extension. Although the task was unrelated to brand extension evaluation, P2 distinguished out-of-category extensions from similar-category and in-category ones, and N400 distinguished similar-category extensions from in-category ones. In experiment 2, a prime–probe paradigm with a related task was used, in which product names included subcategory and major-category product names. The N400 elicited by subcategory products was more significantly negative than that elicited by major-category products, with no salient difference in P2. We speculated that P2 could reflect the early low-level and similarity-based processing in the first stage, whereas N400 could reflect the late analytic and category-based processing in the second stage. [ABSTRACT FROM AUTHOR]

In Parkinson's disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261+ Merck 22; Sch-58261+Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug separately and to determine whether any interaction between two drugs was additive or synergistic. Additional post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered separately at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacological interactions. The combined administration of A2A/NR2B-receptor antagonists improved motor behaviour in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients. [ABSTRACT FROM AUTHOR]

To further characterize the role of frontal and parietal cortices in rat cognition, we recorded action potentials simultaneously from multiple sites in the medio-dorsal frontal cortex and posterior parietal cortex of rats while they performed a two-choice auditory detection task. We quantified neural correlates of task performance, including response movements, perception of a target tone, and the differentiation between stimuli with distinct features (different pitches or durations). A minority of units—15% in frontal cortex, 23% in parietal cortex—significantly distinguished hit trials (successful detections, response movement to the right) from correct rejection trials (correct leftward response to the absence of the target tone). Estimating the contribution of movement-related activity to these responses suggested that more than half of these units were likely signaling correct perception of the auditory target, rather than merely movement direction. In addition, we found a smaller and mostly not overlapping population of units that differentiated stimuli based on task-irrelevant details. The detection-related spiking responses we observed suggest that correlates of perception in the rat are sparsely represented among neurons in the rat's frontal-parietal network, without being concentrated preferentially in frontal or parietal areas. [ABSTRACT FROM AUTHOR]

Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX) to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing) rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates. [ABSTRACT FROM AUTHOR]

While screening a large collection of wild and laboratory yeast strains for their ability to attract Drosophila melanogaster adults, we noticed a large difference in fly preference for two nearly isogenic strains of Saccharomyces cerevisiae, BY4741 and BY4742. Using standard genetic analyses, we tracked the preference difference to the lack of mitochondria in the BY4742 strain used in the initial experiment. We used gas chromatography coupled with mass spectroscopy to examine the volatile compounds produced by BY4741 and the mitochondria-deficient BY4742, and found that they differed significantly. We observed that several ethyl esters are present at much higher levels in strains with mitochondria, even in fermentative conditions. We found that nitrogen levels in the substrate affect the production of these compounds, and that they are produced at the highest level by strains with mitochondria when fermenting natural fruit substrates. Collectively these observations demonstrate that core metabolic processes mediate the interaction between yeasts and insect vectors, and highlight the importance mitochondrial functions in yeast ecology. [ABSTRACT FROM AUTHOR]

Sleep is regulated in a time-of-day dependent manner and profits working memory. However, the impact of the circadian timing system as well as contributions of specific sleep properties to this beneficial effect remains largely unexplored. Moreover, it is unclear to which extent inter-individual differences in sleep-wake regulation depend on circadian phase and modulate the association between sleep and working memory. Here, sleep electroencephalography (EEG) was recorded during a 40-h multiple nap protocol, and working memory performance was assessed by the n-back task 10 times before and after each scheduled nap sleep episode. Twenty-four participants were genotyped regarding a functional polymorphism in adenosine deaminase (rs73598374, 12 G/A-, 12 G/G-allele carriers), previously associated with differences in sleep-wake regulation. Our results indicate that genotype-driven differences in sleep depend on circadian phase: heterozygous participants were awake longer and slept less at the end of the biological day, while they exhibited longer non rapid eye movement (NREM) sleep and slow wave sleep concomitant with reduced power between 8–16 Hz at the end of the biological night. Slow wave sleep and NREM sleep delta EEG activity covaried positively with overall working memory performance, independent of circadian phase and genotype. Moreover, REM sleep duration benefitted working memory particularly when occurring in the early morning hours and specifically in heterozygous individuals. Even though based on a small sample size and thus requiring replication, our results suggest genotype-dependent differences in circadian sleep regulation. They further indicate that REM sleep, being under strong circadian control, boosts working memory performance according to genotype in a time-of-day dependent manner. Finally, our data provide first evidence that slow wave sleep and NREM sleep delta activity, majorly regulated by sleep homeostatic mechanisms, is linked to working memory independent of the timing of the sleep episode within the 24-h cycle. [ABSTRACT FROM AUTHOR]

The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward. [ABSTRACT FROM AUTHOR]

Alarm pheromone and its major component isopentylacetate induce stress-like responses in forager honey bees, impairing their ability to associate odors with a food reward. We investigated whether isopentylacetate exposure decreases appetitive learning also in young worker bees. While isopentylacetate-induced learning deficits were observed in guards and foragers collected from a queen-right colony, learning impairments resulting from exposure to this pheromone could not be detected in bees cleaning cells. As cell cleaners are generally among the youngest workers in the colony, effects of isopentylacetate on learning behavior were examined further using bees of known age. Adult workers were maintained under laboratory conditions from the time of adult emergence. Fifty percent of the bees were exposed to queen mandibular pheromone during this period, whereas control bees were not exposed to this pheromone. Isopentylacetate-induced learning impairments were apparent in young (less than one week old) controls, but not in bees of the same age exposed to queen mandibular pheromone. This study reveals young worker bees can exhibit a stress-like response to alarm pheromone, but isopentylacetate-induced learning impairments in young bees are suppressed by queen mandibular pheromone. While isopentylacetate exposure reduced responses during associative learning (acquisition), it did not affect one-hour memory retrieval. [ABSTRACT FROM AUTHOR]

Cancer and treatments may induce cognitive impairments in cancer patients, and the causal link between chemotherapy and cognitive dysfunctions was recently validated in animal models. New cancer targeted therapies have become widely used, and their impact on brain functions and quality of life needs to be explored. We evaluated the impact of everolimus, an anticancer agent targeting the mTOR pathway, on cognitive functions, cerebral metabolism, and hippocampal cell proliferation/vascular density in mice. Adult mice received everolimus daily for 2 weeks, and behavioral tests were performed from 1 week after the last treatment. Everolimus-treated mice displayed a marked reduction in weight gain from the last day of the treatment period. Ex vivo analysis showed altered cytochrome oxidase activity in selective cerebral regions involved in energy balance, food intake, reward, learning and memory modulation, sleep/wake cycle regulation, and arousal. Like chemotherapy, everolimus did not alter emotional reactivity, learning and memory performances, but in contrast to chemotherapy, did not affect behavioral flexibility or reactivity to novelty. In vivo hippocampal neural cell proliferation and vascular density were also unchanged after everolimus treatments. In conclusion, two weeks daily everolimus treatment at the clinical dose did not evoke alteration of cognitive performances evaluated in hippocampal- and prefrontal cortex-dependent tasks that would persist at one to four weeks after the end of the treatment completion. However, acute everolimus treatment caused selective CO modifications without altering the mTOR effector P70S6 kinase in cerebral regions involved in feeding behavior and/or the sleep/wake cycle, at least in part under control of the solitary nucleus and the parasubthalamic region of the hypothalamus. Thus, this area may represent a key target for everolimus-mediating peripheral modifications, which has been previously associated with symptoms such as weight loss and fatigue. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) is the second leading neurodegenerative disease in the US. As there is no known cause or cure for PD, researchers continue to investigate disease mechanisms and potential new therapies in cell culture and in animal models of PD. In PD, one of the most profoundly affected neuronal populations is the tyrosine hydroxylase (TH)-expressing dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). These DA-producing neurons undergo degeneration while neighboring DA-producing cells of the ventral tegmental area (VTA) are largely spared. To aid in these studies, The Michael J. Fox Foundation (MJFF) partnered with Thomas Jefferson University and Taconic Inc. to generate new transgenic rat lines carrying the human TH gene promoter driving EGFP using a 11 kb construct used previously to create a hTH-GFP mouse reporter line. Of the five rat founder lines that were generated, three exhibited high level specific GFP fluorescence in DA brain structures (ie. SN, VTA, striatum, olfactory bulb, hypothalamus). As with the hTH-GFP mouse, none of the rat lines exhibit reporter expression in adrenergic structures like the adrenal gland. Line 12141, with its high levels of GFP in adult DA brain structures and minimal ectopic GFP expression in non-DA structures, was characterized in detail. We show here that this line allows for anatomical visualization and microdissection of the rat midbrain into SNpc and/or VTA, enabling detailed analysis of midbrain DA neurons and axonal projections after toxin treatment in vivo. Moreover, we further show that embryonic SNpc and/or VTA neurons, enriched by microdissection or FACS, can be used in culture or transplant studies of PD. Thus, the hTH-GFP reporter rat should be a valuable tool for Parkinson's disease research. [ABSTRACT FROM AUTHOR]

Albeit research on brain-computer interfaces (BCI) for controlling applications has expanded tremendously, we still face a translational gap when bringing BCI to end-users. To bridge this gap, we adapted the user-centered design (UCD) to BCI research and development which implies a shift from focusing on single aspects, such as accuracy and information transfer rate (ITR), to a more holistic user experience. The UCD implements an iterative process between end-users and developers based on a valid evaluation procedure. Within the UCD framework usability of a device can be defined with regard to its effectiveness, efficiency, and satisfaction. We operationalized these aspects to evaluate BCI-controlled applications. Effectiveness was regarded equivalent to accuracy of selections and efficiency to the amount of information transferred per time unit and the effort invested (workload). Satisfaction was assessed with questionnaires and visual-analogue scales. These metrics have been successfully applied to several BCI-controlled applications for communication and entertainment, which were evaluated by end-users with severe motor impairment. Results of four studies, involving a total of N = 19 end-users revealed: effectiveness was moderate to high; efficiency in terms of ITR was low to high and workload low to medium; depending on the match between user and technology, and type of application satisfaction was moderate to high. The here suggested evaluation metrics within the framework of the UCD proved to be an applicable and informative approach to evaluate BCI controlled applications, and end-users with severe impairment and in the locked-in state were able to participate in this process. [ABSTRACT FROM AUTHOR]

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions. [ABSTRACT FROM AUTHOR]

Few studies that examine the neurogenesis–behaviour relationship formally establish covariation between neurogenesis and behaviour or rule out competing explanations. The behavioural relevance of neurogenesis might therefore be overestimated if other mechanisms account for some, or even all, of the experimental effects. A systematic review of the literature was conducted and the data reanalysed using causal mediation analysis, which can estimate the behavioural contribution of new hippocampal neurons separately from other mechanisms that might be operating. Results from eleven eligible individual studies were then combined in a meta-analysis to increase precision (representing data from 215 animals) and showed that neurogenesis made a negligible contribution to behaviour (standarised effect  = 0.15; 95% CI  = −0.04 to 0.34; p = 0.128); other mechanisms accounted for the majority of experimental effects (standardised effect  = 1.06; 95% CI  = 0.74 to 1.38; p = 1.7×10−11). [ABSTRACT FROM AUTHOR]

The hippocampus is a structure related to several cognitive processes, but not very much is known about its putative involvement in positive reinforcement. In its turn, the septum has been related to instrumental brain stimulation reward (BSR) by its electrical stimulation with trains of pulses. Although the anatomical relationships of the septo-hippocampal pathway are well established, the functional relationship between these structures during rewarding behaviors remains poorly understood. To explore hippocampal mechanisms involved in BSR, CA3-evoked field excitatory and inhibitory postsynaptic potentials (fEPSPs, fIPSPs) were recorded in the CA1 area during BSR in alert behaving mice. The synaptic efficiency was determined from changes in fEPSP and fIPSP amplitudes across the learning of a BSR task. The successive BSR sessions evoked a progressive increase of the performance in inverse relationship with a decrease in the amplitude of fEPSPs, but not of fIPSPs. Additionally, we evaluated CA1 local field potentials (LFPs) during a preference task, comparing 8-, 20-, and 100-Hz trains of septal BSR. We corroborate a clear preference for BSR at 100 Hz (in comparison with BSR at 20 Hz or 8 Hz), in parallel with an increase in the spectral power of the low theta band, and a decrease in the gamma. These results were replicated by intrahippocampal injections of a GABAB antagonist. Thus, the GABAergic septo-hippocampal pathway seems to carry information involved in the encoding of reward properties, where GABAB receptors seem to play a key role. With regard to the dorsal hippocampus, fEPSPs evoked at the CA3-CA1 synapse seem to reflect the BSR learning process, while hippocampal rhythmic activities are more related to reward properties. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a debilitating disease affecting a wide cross section of people around the world. The current therapy for depression is less than adequate and there is a considerable unmet need for more efficacious treatment. Dopamine has been shown to play a significant role in depression including production of anhedonia which has been one of the untreated symptoms in MDD. It has been hypothesized that drugs acting at all three monoamine transporters including dopamine transporter should provide more efficacious antidepressants activity. This has led to the development of triple reuptake inhibitor D-473 which is a novel pyran based molecule and interacts with all three monoamine transporters. The monoamine uptake inhibition activity in the cloned human transporters expressed in HEK-293 cells (70.4, 9.18 and 39.7 for DAT, SERT and NET, respectively) indicates a serotonin preferring triple reuptake inhibition profile for this drug. The drug D-473 exhibited good brain penetration and produced efficacious activity in rat forced swim test under oral administration. The optimal efficacy dose did not produce any locomotor activation. Microdialysis experiment demonstrated that systemic administration of D-473 elevated extracellular level of the three monoamines DA, 5-HT, and NE efficaciously in the dorsal lateral striatum (DLS) and the medial prefrontal cortex (mPFC) area, indicating in vivo blockade of all three monoamine transporters by D-473. Thus, the current biological data from D-473 indicate potent antidepressant activity of the molecule. [ABSTRACT FROM AUTHOR]