Rodent Behavioral Core: The Analysis of Behavior

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

Behavioral neuroscience links systems-level circuitry to behavior, cognition and emotion and is thus critical for understanding the afflictions that affect neuropsychiatric patients. Linking cognitive changes in a behaving rat or mouse to targeted manipulations of neural circuitry requires the convergence of expertise from scientific fields inside and outside of neuroscience. In designing research projects to understand the anatomy, genetics, and pharmacology underlying the control of behavior, researchers must understand the nature of the task, its measurements, and how to interpret the data. Several steps lie between the design of the experiment and the behavioral output, including choice of task (e.g., operant vs mazes), how to train the animal (shaping vs conditioning), the type of surgical manipulation (ablation, cannulation, inactivation, stimulation, etc.), and the format of data for analysis (summary vs. trial-by-trial). Most neuroscience researchers who use standard off-the-shelf behavioral tasks are not experts in the psychology of behavior and must therefore rely on experts in the domain of cognition. Complex cognitive behavior in rodents is often gauged by measuring the pattern of behavioral responses in tasks that involve, for example, decision-making, attention, memory, rule learning, flexibility, discrimination, and problem solving. In these tasks, rats and mice typically indicate their decisions by nose-poking visual patterns on a touchscreen like an iPad, making nose-poke entries into a series of lit holes, or depressing an extended lever triggered by time or cues. Some cognitive functions extrapolated from animal behavior have positively informed our investigation of cognitive functions in humans. Such animal-to-human approaches (e.g., delayed response) have directed the design and development of analogous tests for use in humans (e.g., self-ordered working memory). Behavioral neuroscience has also benefitted in the opposite direction by means of human-to-animal approaches as in the case of extradimensionsal/intradimensional set shifting, a test based upon the principles of the human Wisconsin Card Sorting Task. Together, these advances in behavioral testing have been particularly useful in establishing the neuroanatomical and neurochemical pathology for specific cognitive deficits in a range of brain and behavior disorders. In addition to providing equipment, training and consulting for researchers interested in using rodents as models to investigate disorders of brain and behavior, one important goal for the rodent behavioral core (RBC) is to continue to design and develop cutting edge behavioral methods and applications while maintaining facility resources at a high level of utility for users at all levels of expertise. This requires constant maintenance and calibration of equipment, user education and interaction, and commitment to setting the standard as the best Rodent Behavioral Core facility in the world in terms of research quality. In the past year, the labs of several principal Investigators from NIMH, as well as NINDS, NIA, NIDCD, NHGRI, NICHD, NIDCD, NEI, and NHLBI have used the RBC to conduct behavioral studies in an efficient and targeted manner. Since opening in 2017, the labs of 51 principal investigators have used the RBC facility with over 100 trainees that have been trained by the RBC staff in some capacity to use specific resources in the Core. Over the past year, we custom designed and developed new tasks to measure various aspects of behavior including providing options for users to assess certain emotional behaviors such as defensive reactions that were more ethologically grounded. We have also instituted a mechanism to record ultrasonic vocalizations from groups of rodent families to measure social communication as an index of emotion. Virtually every piece of equipment in the RBC including operant chambers, mazes and open testing arenas can be is integrated with transistor-transistor logic (TTL) capability to interface with any TTL triggerable piece of equipment or software to enable optogenetic capability. The capability to conduct optogenetic studies in the RBC has made it an invaluable resource for many users who do not have the capability or resources to establish the infrastructure in their own labs. Most recently, we integrated methods of fiber photometry with spatial mazes, operant chambers, and tests of emotional memory to enable users the ability to obtain a more electrophysiological readout. This required updating our operant control systems to enable liquid rewards as well as pellets. In addition, we implemented new LED arrays in operant boxes to provide dim light to measure vision detection thresholds. Finally, due to the high demand for rodent surgery, in the past year we upgraded the surgery suite with an additional Robotic stereotaxic frame to enable high throughout and precision microsurgical procedures. Together, these technical accomplishments have allowed users of the RBC to obtain an in-depth characterization of rodent behavior through modern, automated methods. In addition to providing equipment resources, we have written custom code for several users to enable detailed levels of behavioral quantification or analyses for their experiments. For example, general motor activity data is usually indexed as duration and location of activity. With custom code, weve been able to provide researchers with additional measures such as speed of activity as well as visual patterns of the movement. We have also started to integrate observed behavior with high-speed tracking using DeepLabCut, an open source code computer vision technique to accurately quantify behavior using a pose estimation of body parts. Its major advantage is that it allows the user to go directly from the data set creation to automatic behavioral analysis. It will also provide a means to standardize behavioral testing in an open-access manner so that data generated in the RBC can be shared between collaborators. In the past fiscal year, the scientific supported provided by the NIMH RBC has contributed to several peer reviewed articles published in: Journal of Neuroscience (Jiang et al), International Journal of Molecular Science (Do et al), Cell Reports (Naskar et al; Sathyamurthy et al), Journal of Visual Experiments (Landeck et al), Journal of Parkinsons Disease (Mazza et al), BioRxiv (Mamais et al), Nature (Fernandez et al), Nature Neuroscience (Ma et al) and Communications Biology (Pathak et al).