Behavioral Neuroscience Research Research Articles

Memphis NeuroSTART Program: Promoting Student Success and Increasing the Diversity of Applicants to Neuroscience Graduate Programs.

With grant support from the Research Experience for Undergraduates (REU) program funded by the National Science Foundation (NSF) and the Awards to Stimulate and Support Undergraduate Research Experiences (ASSURE) program funded by the Department of Defense (DoD) Air Force Office of Scientific Research (AFOSR), we established a program intended to increase the number of underrepresented racial and ethnic minority (URM) and first-generation undergraduate students successfully applying to neuroscience and other STEM-related graduate programs. The Neuroscience Techniques and Research Training (NeuroSTART) Program aimed to increase the number of undergraduate students from the Memphis area involved in behavioral neuroscience research. In this two-semester program, students completed an empirical research project in a neuroscience lab, received individual mentoring from neuroscience faculty, became part of a STEM network, presented at research conferences, and attended specialized professional development seminars. In two cohorts of 15 students, 4 are PhD students in neuroscience-related programs or in medical school (27%), 4 are employed in neuroscience-related research facilities (27%), 3 are employed as clinical assistants (20%), and 1 is employed in the IT field (7%). The remaining three recently graduated and are planning a gap year prior to applying for admission to graduate/medical school. The Memphis NeuroSTART program has provided valuable training to participants, making them competitive applicants for jobs in the health sciences and for admittance into graduate neuroscience programs. By providing this training to first-generation and URM students, the broader impact of this program was an increase in the diversity of the health sciences workforce, particularly those specializing in neuroscience-related research and treatment.

High-performance wide-band open-source system for acoustic stimulation

The design and characterization of a low-cost, open-source auditory delivery system to deliver high performance auditory stimuli is presented. The system includes a high-fidelity sound card and audio amplifier devices with low-latency and wide bandwidth targeted for behavioral neuroscience research. The characterization of the individual devices and the entire system is performed, providing a thorough audio characterization data for varying frequencies and sound levels. The system implements the open-source Harp protocol, enabling the hardware timestamping of devices and seamless synchronization with other Harp devices.

Comparison of three DREADD agonists acting on Gq-DREADDs in the ventral tegmental area to alter locomotor activity in tyrosine hydroxylase:Cre male and female rats

RationaleDespite the increasingly pervasive use of chemogenetic tools in preclinical neuroscience research, the in vivo pharmacology of DREADD agonists remains poorly understood. The pharmacological effects of any ligand acting at receptors, engineered or endogenous, are influenced by numerous factors including potency, time course, and receptor selectivity. Thus, rigorous comparison of the potency and time course of available DREADD ligands may provide an empirical foundation for ligand selection. ObjectivesCompare the behavioral pharmacology of three different DREADD ligands clozapine-N-oxide (CNO), compound 21 (C21), and deschloroclozapine (DCZ) in a locomotor activity assay in tyrosine hydroxylase:cre recombinase (TH:Cre) male and female rats. MethodsLocomotor activity in nine adult TH:Cre Sprague-Dawley rats (5 female, 4 male) was monitored for two hours following administration of d-amphetamine (vehicle, 0.1–3.2 mg/kg, IP), DCZ (vehicle, 0.32–320 µg/kg, IP), CNO (vehicle, 0.32–10 mg/kg), and C21 (vehicle, 0.1–3.2 mg/kg, IP). Behavioral sessions were conducted twice per week prior to and starting three weeks after bilateral intra-VTA hM3Dq DREADD virus injection. Resultsd-Amphetamine significantly increased locomotor activity pre- and post-DREADD virus injection. DCZ, CNO, and C21 did not alter locomotor activity pre-DREADD virus injection. There was no significant effect of DCZ, CNO, and C21 on locomotor activity post-DREADD virus injection; however, large individual differences in both behavioral response and receptor expression were observed. ConclusionsLarge individual variability was observed in both DREADD agonist behavioral effects and receptor expression. These results suggest further basic research would facilitate the utility of these chemogenetic tools for behavioral neuroscience research.

Chronotate: An open-source tool for manual timestamping and quantification of animal behavior

A core necessity to behavioral neuroscience research is the ability to accurately measure performance on behavioral assays, such as the novel object location and novel object recognition tasks. These tasks are widely used in neuroscience research and measure a rodent’s instinct for investigating novel features as a proxy to test their memory of a previous experience. Automated tools for scoring behavioral videos can be cost prohibitive and often have difficulty distinguishing between active investigation of an object and simply being in close proximity to an object. As such, many experimenters continue to rely on hand scoring interactions using stopwatches, which makes it difficult to review scoring after-the-fact and results in the loss of temporal information. Here, we introduce Chronotate, a free, open-source tool to aid in manually scoring novel object behavior videos. The software consists of an interactive video player with keyboard integration for marking timestamps of behavioral events during video playback, making it simple to quickly score and review bouts of rodent-object interaction. In addition, Chronotate outputs detailed interaction bout data, allowing for nuanced behavioral performance analyses. Using this detailed temporal information, we demonstrate that novel object location performance peaks within the first 3 s of interaction time and preference for the novel location becomes reduced across the test session. Thus, Chronotate can be used to determine the temporal structure of interactions on this task and can provide new insight into the memory processes that drive this behavior. Chronotate is available for download at: https://github.com/ShumanLab/Chronotate.

Transient strain differences in an operant delayed non-match to position task

Working memory refers to the temporary retention of a small amount of information used in the execution of a cognitive task. Working memory impairments are one of the common hallmarks of many neuropsychiatric and neurological disorders including schizophrenia and Alzheimer’s disease. Here, we investigated Fischer 344 and Long-Evans rats for strain and sex differences in working memory using the operant-based DNMTP task. Rats were required to press one of two levers presented during a sample phase and followed by a 2–32 second delay, the rats were then required to press the opposite, nonmatch, lever during the choice phase. We found a transient strain difference with Fischer 344 rats performing better than Long-Evans early in training. The Fischer 344 strain showed stable performance across sessions while the performance of Long-Evans increased in the later sessions. Since different background rat strains are used for transgenic rat models, it is critical to be able to compare the behavioral performance across different strains. These findings have implications in behavioral neuroscience research as understanding the typical behavioral endpoints in different background strains will aid our understanding of how different models affect behavioral performance.

Incorporating neurological and behavioral mechanisms of sociality into predator-prey models.

Consumer-resource population models drive progress in predicting and understanding predation. However, they are often built by averaging the foraging outcomes of individuals to estimate per capita functional responses (functions that describe predation rate). Reliance on per-capita functional responses rests on the assumption that that individuals forage independently without affecting each other. Undermining this assumption, extensive behavioral neuroscience research has made clear that facilitative and antagonistic interactions among conspecifics frequently alter foraging through interference competition and persistent neurophysiological changes. For example, repeated social defeats dysregulates rodent hypothalamic signaling, modulating appetite. In behavioral ecology, similar mechanisms are studied under the concept of dominance hierarchies. Neurological and behavioral changes in response to conspecifics undoubtedly play some sort of role in the foraging of populations, but modern predator-prey theory does not explicitly include them. Here we describe how some modern approaches to population modeling might account for this. Further, we propose that spatial predator-prey models can be modified to describe plastic changes in foraging behavior driven by intraspecific interaction, namely individuals switching between patches or plastic strategies to avoid competition. Extensive neurological and behavioral ecology research suggests that interactions among conspecifics help shape populations' functional responses. Modeling interdependent functional responses woven together by behavioral and neurological mechanisms may thus be indispensable in predicting the outcome of consumer-resource interactions across systems.

Why help others? Insights from rodent to human early childhood research.

Helping behavior are actions aiming at assisting another individual in need or to relieve their distress. The occurrence of this behavior not only depends on automated physiological mechanisms, such as imitation or emotional contagion, that is, the individual's emotion and physiological state matching with others, but also needs motivation to sustain. From a comparative and developmental perspective, we discover that the motivation for helping behavior has a deep foundation both phylogenetically and ontogenetically. For example, empathic concern for others, relieving personal distress and the desire for social contact are universal motivations across rodents, non-human primates and human early childhoods. Therefore, a circle-layered model integrating evidences for motivation for helping behavior from rodent to human early childhood research is proposed: the inner circle contains the emotional-behavioral system and the outer circle contains the affective-cognitive system. The application of this model has significance for both behavioral neuroscience research and cultivating prosocial behavior in human society.

The boundlessness of behavioral neuroscience: A look across 30 years

It has been more than thirty years since the two inaugural IBNS presidents sat down at a larger neuroscience conference and decided that there should be more to behavioral neuroscience than a single theme at a meeting. The progeny of these conversations is the International Behavioral Neuroscience Society (IBNS) and this year will be its thirty year anniversary. We reflect back on the last thirty years of the research career of the society’s second president, Paul R. Sanberg, as an example of how behavioral neuroscience research has changed these last few decades.

Behavior is movement only but how to interpret it? Problems and pitfalls in translational neuroscience-a 40-year experience.

Translational research in behavioral neuroscience seeks causes and remedies for human mental health problems in animals, following leads imposed by clinical research in psychiatry. This endeavor faces several problems because scientists must read and interpret animal movements to represent human perceptions, mood, and memory processes. Yet, it is still not known how mammalian brains bundle all these processes into a highly compressed motor output in the brain stem and spinal cord, but without that knowledge, translational research remains aimless. Based on some four decades of experience in the field, the article identifies sources of interpretation problems and illustrates typical translational pitfalls. (1) The sensory world of mice is different. Smell, hearing, and tactile whisker sensations dominate in rodents, while visual input is comparatively small. In humans, the relations are reversed. (2) Mouse and human brains are equated inappropriately: the association cortex makes up a large portion of the human neocortex, while it is relatively small in rodents. The predominant associative cortex in rodents is the hippocampus itself, orchestrating chiefly inputs from secondary sensorimotor areas and generating species-typical motor patterns that are not easily reconciled with putative human hippocampal functions. (3) Translational interpretation of studies of memory or emotionality often neglects the ecology of mice, an extremely small species surviving by freezing or flight reactions that do not need much cognitive processing. (4) Further misinterpretations arise from confounding neuronal properties with system properties, and from rigid mechanistic thinking unaware that many experimentally induced changes in the brain do partially reflect unpredictable compensatory plasticity. (5) Based on observing hippocampal lesion effects in mice indoors and outdoors, the article offers a simplistic general model of hippocampal functions in relation to hypothalamic input and output, placing hypothalamus and the supraspinal motor system at the top of a cerebral hierarchy. (6) Many translational problems could be avoided by inclusion of simple species-typical behaviors as end-points comparable to human cognitive or executive processing, and to rely more on artificial intelligence for recognizing patterns not classifiable by traditional psychological concepts.

Timing, neural timescales, and temporal cognition.

This special issue provides a representative snapshot of cutting-edge behavioral neuroscience research on sense of time, cognitive and behavioral functioning, and neural processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pi USB Cam: A Simple and Affordable DIY Solution That Enables High-Quality, High-Throughput Video Capture for Behavioral Neuroscience Research.

Video recording is essential for behavioral neuroscience research, but the majority of available systems suffer from poor cost-to-functionality ratio. Commercial options frequently come at high financial cost that prohibits scalability and throughput, whereas DIY solutions often require significant expertise and time investment unaffordable to many researchers. To address this, we combined a low-cost Raspberry Pi microcomputer, DIY electronics peripherals, freely available open-source firmware, and custom 3D-printed casings to create Pi USB Cam, a simple yet powerful and highly versatile video recording solution. Pi USB Cam is constructed using affordable and widely available components and requires no expertise to build and implement. The result is a system that functions as a plug-and-play USB camera that can be easily installed in various animal testing and housing sites and is readily compatible with popular behavioral and neural recording software. Here, we provide a comprehensive parts list and step-by-step instructions for users to build and implement their own Pi USB Cam system. In a series of benchmark comparisons, Pi USB Cam was able to capture ultra-wide fields of view of behaving rats given limited object distance and produced high image quality while maintaining consistent frame rates even under low-light and no-light conditions relative to a standard, commercially available USB camera. Video recordings were easily scaled using free, open-source software. Altogether, Pi USB Cam presents an elegant yet simple solution for behavioral neuroscientists seeking an affordable and highly flexible system to enable quality video recordings.

Assessing the importance of sex in a hippocampus-dependent behavioral test battery in C57BL/6NTac mice.

Inclusion of male and female subjects in behavioral neuroscience research requires a concerted effort to characterize sex differences in standardized behavioral assays. Sex differences in hippocampus-dependent assays have been widely reported but are still poorly characterized. In the present study, we conducted a parametric analysis of spontaneous alternation, object recognition, and fear conditioning in a commonly used control strain, C57BL/6NTac. Our findings show largely similar performance between males and females across the majority of behavioral end points. However, we identified an important difference in nonassociative fear sensitization, whereby females showed an enhanced fear response to the 75-dB tone that is used as the conditional stimulus. In addition, we observed an impairment in object location performance in females that was ameliorated by more extensive habituation to handling. Together, these findings argue that sex differences in nonassociative fear responses to both novel auditory cues and novel objects need to be considered when designing and interpreting cognitive assays in C57BL/6 mice. Furthermore, this elevated fear sensitization could serve as a novel approach to model the increased incidence of anxiety disorders in women.

Dynamic effects of dietary protein restriction on body weights, food consumption, and protein preference in C57BL/6J and Fgf21-KO mice.

Single-case experimental designs (SCEDs) are rarely used in behavioral neuroscience despite their potential benefits. The current study used a SCED to evaluate the effects of dietary protein restriction in C57BL/6J and Fgf21-knockout (KO) mice on body weight, food consumption, and protein preference and changes in those outcome measures were quantified using multilevel linear models. In C57BL/6J mice, rate of weight gain was lower and food consumption and protein preference higher during periods of low (4% kcal) protein diet feeding compared to periods of normal (18% kcal) protein diet feeding. In Fgf21-KO mice, who do not produce the liver-derived hormone FGF21, rate of weight gain and protein preference were not substantially affected by diet although food consumption was slightly higher during periods of low protein diet than periods of normal protein diet. These results demonstrate that protein restriction dynamically regulates physiological and behavioral responses at the individual mouse level and that FGF21 is necessary for those responses. Further, the current results demonstrate how a SCED can be used in behavioral neuroscience research, which entails both scientific and practical benefits.

Elements of a compound elicit little conditioned reinforcement.

The acquisition of instrumental responding can be supported by primary reinforcers or by conditional (also known as secondary) reinforcers that themselves have an association to a primary reinforcer. While primary reinforcement has been heavily studied for the past century, the associative basis of conditioned reinforcement has received comparatively little experimental examination. Yet conditioned reinforcement has been employed as an important behavioral assay in neuroscience studies, and thus an analysis of its associative basis is called for. We evaluated the extent to which an element from a previously trained compound would facilitate conditioned reinforcement. Three groups of rats received Pavlovian conditioning with a visual-auditory compound cue followed by food. After training, a lever was made available that, when pressed, produced the same trained compound (group compound), only the auditory cue (group element), or a novel auditory cue (group control). The rats in group compound pressed the lever at a higher rate than did rats in either group element or group control, demonstrating a strong conditioned reinforcement effect only in group compound. Interestingly, there was almost no difference in responding between group element and group control. The implications of this generalization decrement in conditioned reinforcement are discussed-particularly as they relate to research in behavioral neuroscience. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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 (c) 2021 APA, all rights reserved).

Wireless and battery-free technologies for neuroengineering.

Tethered and battery-powered devices that interface with neural tissues can restrict natural motions and prevent social interactions in animal models, thereby limiting the utility of these devices in behavioural neuroscience research. In this Review Article, we discuss recent progress in the development of miniaturized and ultralightweight devices as neuroengineering platforms that are wireless, battery-free and fully implantable, with capabilities that match or exceed those of wired or battery-powered alternatives. Such classes of advanced neural interfaces with optical, electrical or fluidic functionality can also combine recording and stimulation modalities for closed-loop applications in basic studies or in the practical treatment of abnormal physiological processes.

Impaired discriminative avoidance and increased plasma corticosterone levels induced by vaginal lavage procedure in rats

Historically, females have been neglected in behavioral neuroscience research due to the alleged increased variability caused by hormonal fluctuations. More recently, there has been a tendency to include female subjects in the studies, in a majority of those cases with the condition that the hormonal variation is controlled. In rodent studies, the vaginal lavage procedure is a common method of collecting smears and determining the estrous cycle phase. However, little is known regarding the consequences of the procedure, although stress is often mentioned as a concern. Within the neuroscience field, spatial memory has been a relevant subject in terms of sex differences. The plus-maze discriminative avoidance task (PMDAT) allows for the concomitant evaluation of spatial memory, anxiety-like behavior, and locomotion, as well as possible interactions between these behaviors. The aim of the present study was to investigate the effects of the vaginal lavage procedure (VLP) on the performance of female rats in the PMDAT. We submitted adult female Wistar rats to VLP for 14 straight days and then to training and test sessions in the PMDAT. Additionally, another set of animals was submitted to the VLP procedure for determination of plasma corticosterone levels. Rats submitted to the vaginal lavage procedure did not discriminate the enclosed arms of the PMDAT apparatus, indicating impaired performance, but no anxiety-like alterations were found. VLP also resulted in a higher corticosterone level, suggesting it is a stressful manipulation. As such, the use of this method to control for hormonal variation should be restricted in behavioral studies.

Importance of Zebrafish as an Efficient Research Model for the Screening of Novel Therapeutics in Neurological Disorders.

Over the previous years, the use of an animal model has become very common for the screening of novel drugs. Animal model represents the complex problems of humans into the simplest forms, so these can be extended further to be included in the experimental procedure. The most successful models in neuroscience, rats and mice, are undoubtedly considered as one of the best models to understand the psychology of the mammalian brain and its associated functions involved in behavioral repertoire. Moreover, recently researchers in behavioral neuroscience are focusing more on the use of aquatic animals, especially fish, as model species due to their simplicity and cost-effectiveness. Zebrafish (Danio rerio) is a tropical fish from the minnow family, a genetic structure surprisingly 84% similar to humans. It is gaining popularity as a model to study the mechanism in behavioral neuropharmacology. Moreover, zebrafish has numerous advantages over other rodent models like the ease in maintenance due to their small size, more breeding power, transparency of embryos, overall reduced cost of experimentation, and many more. Nowadays, it is considered an ideal model to study the neurobehavioral aspects with relevance to humans. It is also used in a variety of scientific studies like genetics, neuroscience, pharmacology, and toxicology. In this manuscript, we have described the feasibility and importance of zebrafish as a model for the screening of novel drugs for different neurological disorders.

Single-case experimental designs for behavioral neuroscience.

Single-case experimental designs (SCEDs) are commonly used in behavior analytic research but rarely used in behavioral neuroscience research. The recent development of technologies that allow control of the timing of neurobiological events such as gene expression and neuronal firing enable the fruitful application of SCEDs for the study of brain-behavior relations. There are at least 3 benefits expected from applying SCEDs to study how neurobiological events affect behavior. First, SCEDs entail direct within- and across-subject assessments of reliability, likely increasing the probability of replication across studies and encouraging a search for the causes of replication failure when they occur. Second, SCEDs focus on behavior in individual organisms producing a body of knowledge that applies to individuals rather than population parameters. Finally, SCEDs require fewer animals, decreasing costs and effort and addressing the ethical obligation to reduce the number of animals used for research. Examples are provided using hypothetical data generated based on published research. Collaborations between behavior analysts and behavioral neuroscientists will bring the world within the skin under direct experimental control and broaden our understanding of the determinants of behavior.

Braitenberg Vehicles as Computational Tools for Research in Neuroscience.

Valentino Braitenberg reported his seminal thought experiment in 1984 using reactive automatons or vehicles with relatively simple sensorimotor connections as models for seemingly complex cognitive processes in biological brains. Braitenberg's work, meant as a metaphor for biological life encompassed a deep knowledge of and served as an analogy for the multitude of neural processes and pathways that underlie animal behavior, suggesting that seemingly complex behavior may arise from relatively simple designs. Braitenberg vehicles have been adopted in robotics and artificial life research for sensor-driven navigation behaviors in robots, such as localizing sound and chemical sources, orienting toward or away from current flow under water etc. The neuroscience community has benefitted from applying Braitenberg's bottom-up approach toward understanding analogous neural mechanisms underpinning his models of animal behavior. We present a summary of the latest studies of Braitenberg vehicles for bio-inspired navigation and relate the results to experimental findings on the neural basis of navigation behavior in animals. Based on these studies, we motivate the important role of Braitenberg vehicles as computational tools to inform research in behavioral neuroscience.