Behavioral Neuroscience Research Research Articles

Does Brain Lateralization Affect the Performance in Binary Choice Tasks? A Study in the Animal Model Danio rerio

Researchers in behavioral neuroscience commonly observe the behavior of animal subjects in the presence of two alternative stimuli. However, this type of binary choice introduces a potential confound related to side biases. Understanding whether subjects exhibit this bias, and the origin of it (pre-existent or acquired throughout the experimental sessions), is particularly important to interpreting the results. Here, we tested the hypothesis according to which brain lateralization may influence the emergence of side biases in a well-known model of neuroscience, the zebrafish. As a measure of lateralization, individuals were observed in their spontaneous tendencies to monitor a potential predator with either the left or the right eye. Subjects also underwent an operant conditioning task requiring discrimination between two colors placed on the left–right axis. Although the low performance exhibited in the operant conditioning task prevents firm conclusions from being drawn, a positive correlation was found between the direction of lateralization and the tendency to select the stimulus presented on one specific side (e.g., right). The choice for this preferred side did not change throughout the experimental sessions, meaning that this side bias was not the result of the prolonged training. Overall, our study calls for a wider investigation of pre-existing lateralization biases in animal models to set up methodological counterstrategies to test individuals that do not properly work in a binary choice task with stimuli arranged on the left–right axis.

Sense and Sensibility: A Review of the Behavioral Neuroscience of Tinnitus Sound Therapy and a New Typology.

Tinnitus Sound Therapy is not a single strategy. It consists of many different sound types, targeting many different mechanisms. Therapies that use sound to cover, reduce attention to, or facilitate habituation of tinnitus are among the most common tinnitus treatment paradigms. Recent history has seen a proliferation of sound therapies, but they have each been criticized for having limited empirical support. In this review, Sound Therapy's modern history will be described, and a typology will be introduced and discussed in light of current behavioral neuroscience research. It will be argued that contributing factors to the limited evidence for the efficacy of Sound Therapy are its diversity, plural modes of action, and absence of a clear typology. Despite gaps in understanding the efficacy of sound's effects on tinnitus, there is compelling evidence for its multiple, but related, neurophysiological mechanisms. Evidence suggests that sound may reduce tinnitus through its presence, context, reaction, and potentially adaptation. This review provides insights into the neurocognitive basis of these tinnitus Sound Therapy modes. It concludes that a unifying classification is needed to secure and advance arguments in favor of Sound Therapy.

Repeated ethanol exposure increases anxiety-like behaviour in zebrafish during withdrawal.

Zebrafish (Danio rerio) are quickly becoming an important model organism in behavioural neuroscience and drug addiction research. Conditioned place preference studies show that drugs of abuse produce responses in zebrafish that are similar to mammalian animal models. Repeated administration of ethanol in zebrafish results in withdrawal-induced behavioural responses that vary with dose and exposure duration, requiring additional investigation. Here, we examine the effects of ethanol withdrawal on anxiety-like behaviours in adult zebrafish after a 21-day ethanol dosing schedule at either 0.4% or 0.8%. Anxiety-like behaviour was measured with the novel object approach test; this test involves placing a fish in a circular arena with a novel object in the centre and observing the amount of exploration of the object. We found increased anxiety-like behaviour during ethanol withdrawal. This study adds to the growing body of literature that validates the zebrafish as a model organism in the field of behavioural neuroscience and addiction.

Rigor and reproducibility in rodent behavioral research.

Behavioral neuroscience research incorporates the identical high level of meticulous methodologies and exacting attention to detail as all other scientific disciplines. To achieve maximal rigor and reproducibility of findings, well-trained investigators employ a variety of established best practices. Here we explicate some of the requirements for rigorous experimental design and accurate data analysis in conducting mouse and rat behavioral tests. Novel object recognition is used as an example of a cognitive assay which has been conducted successfully with a range of methods, all based on common principles of appropriate procedures, controls, and statistics. Directors of Rodent Core facilities within Intellectual and Developmental Disabilities Research Centers contribute key aspects of their own novel object recognition protocols, offering insights into essential similarities and less-critical differences. Literature cited in this review article will lead the interested reader to source papers that provide step-by-step protocols which illustrate optimized methods for many standard rodent behavioral assays. Adhering to best practices in behavioral neuroscience will enhance the value of animal models for the multiple goals of understanding biological mechanisms, evaluating consequences of genetic mutations, and discovering efficacious therapeutics.

Use of TAI-FISH to visualize neural ensembles activated by multiple stimuli.

Researchers in behavioral neuroscience have long sought imaging techniques that can identify and distinguish neural ensembles that are activated by sequentially applied stimuli at single-cell resolution across the whole brain. Taking advantage of the different kinetics of immediate-early genes' mRNA and protein expression, we addressed this problem by developing tyramide-amplified immunohistochemistry-fluorescence in situ hybridization (TAI-FISH), a dual-epoch neural-activity-dependent labeling protocol. Here we describe the step-by-step procedures for TAI-FISH on brain sections from mice that were sequentially stimulated by morphine (appetitive first stimulus) and foot shock (aversive second stimulus). We exemplify our approach by FISH-labeling the neural ensembles that were activated by the second stimulus for the mRNA expression of c-fos, a well-established marker of neural activation. We labeled neuronal ensembles activated by the first stimulus using fluorescence immunohistochemistry (IHC) for the c-fos protein. To further improve the temporal separation of the c-fos mRNA and protein signals, we provide instructions on how to enhance the protein signals using tyramide signal amplification (TSA). Compared with other dual-epoch labeling techniques, TAI-FISH provides better temporal separation of the activated neural ensembles and is better suited to investigation of whole-brain responses. TAI-FISH has been used to investigate neural activation patterns in response to appetitive and aversive stimuli, and we expect it to be more broadly utilized for visualizing brain responses to other types of stimuli, such as sensory stimuli or psychiatric drugs. From first stimulation to image analysis, TAI-FISH takes ∼9 d to complete.

Optogenetic Inhibition Reveals Distinct Roles for Basolateral Amygdala Activity at Discrete Time Points during Risky Decision Making

Decision making is a multifaceted process, consisting of several distinct phases that likely require different cognitive operations. Previous work showed that the basolateral amygdala (BLA) is a critical substrate for decision making involving risk of punishment; however, it is unclear how the BLA is recruited at different stages of the decision process. To this end, the current study used optogenetics to inhibit the BLA during specific task phases in a model of risky decision making (risky decision-making task) in which rats choose between a small, "safe" reward and a large reward accompanied by varying probabilities of footshock punishment. Male Long-Evans rats received intra-BLA microinjections of viral vectors carrying either halorhodopsin (eNpHR3.0-mCherry) or mCherry alone (control) followed by optic fiber implants and were trained in the risky decision-making task. Laser delivery during the task occurred during intertrial interval, deliberation, or reward outcome phases, the latter of which was further divided into the three possible outcomes (small, safe; large, unpunished; large, punished). Inhibition of the BLA selectively during the deliberation phase decreased choice of the large, risky outcome (decreased risky choice). In contrast, BLA inhibition selectively during delivery of the large, punished outcome increased risky choice. Inhibition had no effect during the other phases, nor did laser delivery affect performance in control rats. Collectively, these data indicate that the BLA can either inhibit or promote choice of risky options, depending on the phase of the decision process in which it is active.SIGNIFICANCE STATEMENT To date, most behavioral neuroscience research on neural mechanisms of decision making has used techniques that preclude assessment of distinct phases of the decision process. Here we show that optogenetic inhibition of the BLA has opposite effects on choice behavior in a rat model of risky decision making, depending on the phase in which inhibition occurs. BLA inhibition during a period of deliberation between small, safe and large, risky outcomes decreased risky choice. In contrast, BLA inhibition during receipt of the large, punished outcome increased risky choice. These findings highlight the importance of temporally targeted approaches to understand neural substrates underlying complex cognitive processes. More importantly, they reveal novel information about dynamic BLA modulation of risky choice.

An automated system for positive reinforcement training of group-housed macaque monkeys at breeding and research facilities

BackgroundBehavioural training through positive reinforcement techniques is a well-recognised refinement to laboratory animal welfare. Behavioural neuroscience research requires subjects to be trained to perform repetitions of specific behaviours for food/fluid reward. Some animals fail to perform at a sufficient level, limiting the amount of data that can be collected and increasing the number of animals required for each study. New methodWe have implemented automated positive reinforcement training systems (comprising a button press task with variable levels of difficulty using LED cues and a fluid reward) at the breeding facility and research facility, to compare performance across these different settings, to pre-screen animals for selection and refine training protocols. ResultsAnimals learned 1- and 4-choice button tasks within weeks of home enclosure training, with some inter-individual differences. High performance levels (∼200–300 trials per 60min session at ∼80% correct) were obtained without food or fluid restriction. Moreover, training quickly transferred to a laboratory version of the task. Animals that acquired the task at the breeding facility subsequently performed better both in early home enclosure sessions upon arrival at the research facility, and also in laboratory sessions. Comparison with existing method(s)Automated systems at the breeding facility may be used to pre-screen animals for suitability for behavioural neuroscience research. In combination with conventional training, both the breeding and research facility systems facilitate acquisition and transference of learning. ConclusionsAutomated systems have the potential to refine training protocols and minimise requirements for food/fluid control.

Common marmoset (Callithrix jacchus) as a primate model for behavioral neuroscience studies

BackgroundThe common marmoset (Callithrix jacchus) has been proposed as a suitable bridge between rodents and larger primates. They have been used in several types of research including auditory, vocal, visual, pharmacological and genetics studies. However, marmosets have not been used as much for behavioral studies. New methodHere we present data from training 12 adult marmosets for behavioral neuroscience studies. We discuss the husbandry, food preferences, handling, acclimation to laboratory environments and neurosurgical techniques. In this paper, we also present a custom built “scoop” and a monkey chair suitable for training of these animals. ResultsThe animals were trained for three tasks: 4 target center-out reaching task, reaching tasks that involved controlling robot actions, and touch screen task. All animals learned the center-out reaching task within 1–2 weeks whereas learning reaching tasks controlling robot actions task took several months of behavioral training where the monkeys learned to associate robot actions with food rewards. Comparison to existing methodWe propose the marmoset as a novel model for behavioral neuroscience research as an alternate for larger primate models. This is due to the ease of handling, quick reproduction, available neuroanatomy, sensorimotor system similar to larger primates and humans, and a lissencephalic brain that can enable implantation of microelectrode arrays relatively easier at various cortical locations compared to larger primates. ConclusionAll animals were able to learn behavioral tasks well and we present the marmosets as an alternate model for simple behavioral neuroscience tasks.

DREADDS: Use and application in behavioral neuroscience.

Technological advances over the last decade are changing the face of behavioral neuroscience research. Here we review recent work on the use of one such transformative tool in behavioral neuroscience research, chemogenetics (or Designer Receptors Exclusively Activated by Designer Drugs, DREADDS). As transformative technologies such as DREADDs are introduced, applied, and refined, their utility in addressing complex questions about behavior and cognition becomes clear and exciting. In the behavioral neuroscience field, remarkable new findings now regularly appear as a result of the ability to monitor and intervene in neural processes with high anatomical precision as animals behave in complex task environments. As these new tools are applied to behavioral questions, individualized procedures for their use find their way into diverse labs. Thus, "tips of the trade" become important for wide dissemination not only for laboratories that are using the tools but also for those who are interested in incorporating them into their own work. Our aim is to provide an up-to-date perspective on how the DREADD technique is being used for research on learning and memory, decision making, and goal-directed behavior, as well as to provide suggestions and considerations for current and future users based on our collective experience. (PsycINFO Database Record

A Simple Method for Immunohistochemical Staining of Zebrafish Brain Sections for c-fos Protein Expression.

Immediate early genes (IEGs) are transcription factors whose own transcription is initiated rapidly, for example, in the brain in response to environmental stimuli. c-fos is an IEG often used as a marker of neuronal activation. c-fos mRNA expression has started to be quantified and localized in the zebrafish brain following environmental manipulations but analysis of the expression of c-fos protein in the zebrafish brain has rarely been attempted. Here, we describe an immunofluorescence staining method for quantifying c-fos protein expression in different regions of the zebrafish brain. In addition, we expose zebrafish to caffeine, a positive control for c-fos activation in the brain. To confirm cell nucleus specific binding of the c-fos antibody, we counterstained brain sections with the nuclear fluorescent stain DAPI. Furthermore, we describe a method for reducing background autofluorescence often observed in zebrafish brain tissue. Our analysis showed that exposure to caffeine increased the number of c-fos protein-positive cells in specific zebrafish brain regions detected by the immunofluorescence method. Our results demonstrate the feasibility of immunofluorescence-based methods in the analysis of neuronal activation in the zebrafish brain, and reinforce the utility of the zebrafish in behavioral neuroscience research.

When Punishment Doesn’t Pay: Cold Glow and Decisions to Punish

Economic theories of punishment focus on determining the levels that provide maximal social material payoffs. In other words, these theories treat punishment as a public good. Several parameters are key to calculating optimal levels of punishment: total social costs, total social benefits, and the probability that offenders are apprehended. However, levels of punishment are often determined by aggregating individual decisions. Research in behavioral economics, psychology, and neuroscience shows that individuals appear to treat punishment as a private good (cold glow). This means that individual choices may not respond appropriately to the social parameters. We present a simple theory and show in a series of experiments that individually chosen punishment levels can be predictably too high or too low relative to those that maximize social material welfare. Our findings highlight the importance of the psychology of punishment for under-standing social outcomes and for designing social institutions.

Wireless Optogenetics: An Exploration of Portable Microdevices for Small Animal Photostimulation

Preclinical research in optogeneticneuromodulation in small laboratory animals allows far greater control of neural circuitry. This precision provides an enhanced opportunity for understanding the neural basis of behavior. However, behavioral neuroscience research is limited by conventional benchtop optogenetic systems. By necessity, the animal is tethered to the light source external to the testing environment. Portable optogeneticmicrodevices enhance the potential for valid behavioral testing in naturalistic conditions by eliminating tethering and enabling free and unrestricted movement. This paper reviews recent advances in the development of portable optogeneticmicrodevices supported by wireless power transfer. Light sources and fiber coupling are common problems in optogenetic systems and are addressed. Device designs and parameters are summarized, along with advances in component technology for energy storage and distribution that make these devices possible.

Ethical Issues in Behavioral Neuroscience : Ethics of Human Research in Behavioral Neuroscience: Overview of Section II.

Section I. Experimental Animal Research.- Ethical Issues Associated with the Use of Animal Experimentation in Behavioural Neuroscience Research.- The use of animal models in behavioural neuroscience research.- Does the goal justify the methods? Harm and Benefit in Neuroscience Research Using Animals.- A Framework for investigating animal consciousness.- Telos, Conservation of Welfare, and Ethical Issues in Genetic Engineering of Animals.- Would the elimination of the capacity to suffer evolve ethical dilemmas in experimental animal research?.- Section II. Clinical Research.- Ethics of human research in behavioral neuroscience: Overview of section II.- What's special about the ethical challenges of studying disorders with altered brain activity?.- Effects of brain injury on moral agency: Ethical dilemmas in investigating human behavior.- Genetic testing and neuroimaging for youth at risk for mental illness: Trading off benefit and risk.- Externalization of consciousness: Scientific possibilities and clinical implications.- How does enhancing cognition affect human values? How does this translate into social responsibility?.- Deep brain stimulation: A principled and pragmatic approach to understanding the ethical and clinical challenges of an evolving technology.- Ethical issues and ethical therapy associated with anxiety disorders.- Just like a circus: The public consumption of sex differences.- Money and morals: Ending clinical trials for financial reasons.

The use of animal models in behavioural neuroscience research.

Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are also likely to be considered the ones that are most morally problematic to use, if it seems probable that (and if indeed they are initially selected as models because) they have experiences that are similar to human experiences that we have strong reasons to avoid causing, and indeed aim to alleviate (such as pain, anxiety or sadness). In this paper, against the background of contemporary discussions in animal ethics and the philosophy of animal minds, we discuss the views that it is morally permissible to use animals in these kinds of experiments, and that it is better to use less cognitively complex animals (such as zebrafish) than more complex animals (such as dogs). First, we criticise some justifications for the claim that human beings and more complex animals have higher moral status. We argue that contemporary approaches that attribute equal moral status to all beings that are capable of conscious strivings strivings (e.g. avoiding pain and anxiety; aiming to eat and play) are based on more plausible assumptions. Second, we argue that it is problematic to assume that less cognitively complex animals have a lesser sensory and emotional experience than more complex beings across the board. In specific cases, there might be good reasons to assume that more complex beings would be harmed more by a specific physical or environmental intervention, but it might also be that they sometimes are harmed less because of a better ability to cope. Determining whether a specific experiment is justified is therefore a complex issue. Our aim in this chapter is to stimulate further reflection on these common assumptions behind the use of animal models for psychopathologies. In order to be able to draw more definite conclusions, more research will have to be done on the influence of cognitive complexity on the experience of (human and non-human) animals.

Dopamine Modulates Risk-Taking as a Function of Baseline Sensation-Seeking Trait

Trait sensation-seeking, defined as a need for varied, complex, and intense sensations, represents a relatively underexplored hedonic drive in human behavioral neuroscience research. It is related to increased risk for a range of behaviors including substance use, gambling, and risky sexual practice. Individual differences in self-reported sensation-seeking have been linked to brain dopamine function, particularly at D2-like receptors, but so far no causal evidence exists for a role of dopamine in sensation-seeking behavior in humans. Here, we investigated the effects of the selective D2/D3 agonist cabergoline on performance of a probabilistic risky choice task in healthy humans using a sensitive within-subject, placebo-controlled design. Cabergoline significantly influenced the way participants combined different explicit signals regarding probability and loss when choosing between response options associated with uncertain outcomes. Importantly, these effects were strongly dependent on baseline sensation-seeking score. Overall, cabergoline increased sensitivity of choice to information about probability of winning; while decreasing discrimination according to magnitude of potential losses associated with different options. The largest effects of the drug were observed in participants with lower sensation-seeking scores. These findings provide evidence that risk-taking behavior in humans can be directly manipulated by a dopaminergic drug, but that the effectiveness of such a manipulation depends on baseline differences in sensation-seeking trait. This emphasizes the importance of considering individual differences when investigating manipulation of risky decision-making, and may have relevance for the development of pharmacotherapies for disorders involving excessive risk-taking in humans, such as pathological gambling.

Functional Magnetic Resonance Imaging (fMRI) with Auditory Stimulation in Songbirds

The neurobiology of birdsong, as a model for human speech, is a pronounced area of research in behavioral neuroscience. Whereas electrophysiology and molecular approaches allow the investigation of either different stimuli on few neurons, or one stimulus in large parts of the brain, blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) allows combining both advantages, i.e. compare the neural activation induced by different stimuli in the entire brain at once. fMRI in songbirds is challenging because of the small size of their brains and because their bones and especially their skull comprise numerous air cavities, inducing important susceptibility artifacts. Gradient-echo (GE) BOLD fMRI has been successfully applied to songbirds (1-5) (for a review, see (6)). These studies focused on the primary and secondary auditory brain areas, which are regions free of susceptibility artifacts. However, because processes of interest may occur beyond these regions, whole brain BOLD fMRI is required using an MRI sequence less susceptible to these artifacts. This can be achieved by using spin-echo (SE) BOLD fMRI (7,8) . In this article, we describe how to use this technique in zebra finches (Taeniopygia guttata), which are small songbirds with a bodyweight of 15-25 g extensively studied in behavioral neurosciences of birdsong. The main topic of fMRI studies on songbirds is song perception and song learning. The auditory nature of the stimuli combined with the weak BOLD sensitivity of SE (compared to GE) based fMRI sequences makes the implementation of this technique very challenging.

When Punishment Doesn't Pay: 'Cold Glow' and Decisions to Punish

Economic theories of punishment focus on determining the levels that provide maximal social material payoffs. In calculating these levels several parameters are key: total social costs, total social benefits and the probability that offenders are apprehended. However, levels of punishment often are determined by aggregates of individual decisions. Research in behavioral economics, psychology and neuroscience shows that individuals appear to treat punishment as a private good (“cold glow”). Thus individual choices may not respond “appropriately” to the parameters above. This can have large consequences: realized punishment levels can be predictably above or below those that maximize aggregate material payoffs. Such behavior can lead to inefficiencies in final social outcomes such as levels of cooperation and total costs incurred. We confirm these predictions in a series of experiments. Our findings highlight the importance of the psychology of punishment for understanding social outcomes and for designing social mechanisms, for example in sentencing policy.

GEBIN 2013 Sponsors

The intracarotid sodium amobarbital procedure (IAP) is currently regarded as the best method for the determination of hemispheric specialization for speech, and it is universally relied on as a prognostic test for patients with medically refractory epilepsy who are candidates for neurosurgical intervention. Since its initial development, the IAP also has been adapted for assesssing lateralized mesiotemporal contributions to memory functioning in this patient population, and it is now in wide use for both basic and applied research in behavioral neuroscience on language, memory, visuospatial functions, emotion, attention, and consciousness. Despite the IAP's wide range of applications, little has been said about its history and development. This essay recounts and discusses this history.

Coping changes the brain

One of the earliest and most consistent findings in behavioral neuroscience research is that learning changes the brain. Here we consider how learning as an aspect of coping in the context of stress exposure induces neuroadaptations that enhance emotion regulation and resilience. A systematic review of the literature identified 15 brain imaging studies in which humans with specific phobias or post-traumatic stress disorder (PTSD) were randomized to stress exposure therapies that diminished subsequent indications of anxiety. Most of these studies focused on functional changes in the amygdala and anterior corticolimbic brain circuits that control cognitive, motivational, and emotional aspects of physiology and behavior. Corresponding structural brain changes and the timing, frequency, and duration of stress exposure required to modify brain functions remain to be elucidated in future research. These studies will advance our understanding of coping as a learning process and provide mechanistic insights for the development of new interventions that promote stress coping skills.

Understanding stress resilience

Understanding stress resilience