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| The Mouse That Roared: Critical Roles for Behavior Analysis in the Genetic Revolution |
| Monday, May 31, 2010 |
| 3:30 PM–4:50 PM |
| Lone Star Ballroom Salon D (Grand Hyatt) |
| Area: EAB/AAB; Domain: Experimental Analysis |
| Chair: Jonathan W. Pinkston (UT Health Science Center at San Antonio) |
| Abstract: Advances in genetic and molecular sciences have introduced unprecedented ability to investigate gene-related risk factors of human disease. In particular, genetically altered animals are among the most promising developments to have emerged in recent years. At present, there are over 3,000 genetically altered mouse types available for study. Clearly, the interest in the development of valid mouse preparations represents an enormous research effort. But what is the role for Behavior Analysis in this effort? In some ways, research into behavioral processes with mice has passed by our field. Some researchers seem content to rely on simple sensorimotor tasks to characterize “learning and memory” and some have suggested that operant preparations are simply not suitable to the study of mice. The goal of this symposium is to demonstrate the relevance of behavior analysis to the study of gene-environment-behavior interactions by providing examples from current research. Each of the authors brings data indicating that behavior analysis stands to be important to research in genetically altered mice. Behavior analysis is positioned uniquely to examine the impact of genetic manipulations at the level of the whole organism; a capability that makes our field essential to fulfilling the promises of genetic and molecular science. |
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| Assessing Discounting in Adolescent and Adult Mice: Strain-Related Differences in Life-Persistent Impulsivity |
| JONATHAN W. PINKSTON (UT Health Science Center at San Antonio), R.J. Lamb (University of Texas HSC-H) |
| Abstract: Adolescence is a developmental period characterized by risky choices and impulsive decision making. For most people, impulsivity is lost as the person matures, but for a few, adolescent impulsivity persists into adulthood and is associated with a variety of externalizing disorders. Murine models offer powerful resources for exploration and identification of genetic factors that may increase the risk for impulsive behavior during adolescence and adulthood. In the present experiment, we examined delay discounting characteristics in adolescent and adult C57BL/6J and DBA/D2 mice using a rapid assessment procedure that can be completed in two weeks. During the first week, mice could choose between 0.02-ml or 0.1-ml volume of milk, each delayed by 1 second. During the second week, the delay to the larger volume was systematically increased from 1 to 100 seconds. During the first week, mice from all strains preferred the larger volume of milk over the smaller volume. When the delay to the large volume increased, preference for the small volume increased. Shifts in preference were similar for adolescent mice in both strains. For adult mice, however, the shift in preference developed more slowly for C57 mice compared to DBA mice. In fact, shifts in preference for DBA mice occurred at approximately the same rate as adolescent mice. The data indicate that DBA mice are characterized by impulsive choice patterns that persist into adulthood, while C57 mice show a reduction in impulsivity across developmental time. |
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| Thinking Outside the (Skinner) Box: The Evolution of the Experimental Analysis of (Mouse) Behavior |
| TROY J. ZARCONE (University of Rochester Medical Center) |
| Abstract: Advances in genetics and proteomics are leading to new discoveries about the central nervous system (CNS). The experimental analysis of behavior can become a leading force in guiding these newer sciences towards their promise of scientific understanding and medical advances. To influence these other sciences the experimental analysis of behavior must also evolve to deal with the model species these other sciences depend on. The genetically defined or modified mouse presents many challenges to the procedures and technologies established for the laboratory rat. The present experiment describes one approach to designing quantitative high-throughput screening apparatus and procedures to examine differences between Cln3 wildtype (WT) and Cln3 knockout (KO) mice. The results showed that Cln3 KO perform differently from WT mice in a operant response-holding task, that was trained with an auto-shaping procedure, with an expanded measurement technique. This simple operant task may be a potential method for measuring "learning and memory" deficits in genetically defined mice. Continued development of computer controlled environments and expansion of measurement beyond response rate, may lead to a renewed interest in operant procedures by other scientific disciplines. |
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| Strain and Species Differences in an Incremental Repeated Acquisition Procedure |
| JORDAN M. BAILEY (Auburn University), Jennifer M. Johnson (Auburn University), Kristen Amanda Spencer (Auburn University), M. Christopher Newland (Auburn University) |
| Abstract: Genetic predispositions may produce environment-behavior interactions that influence the acquisition of complex behavior. Learning was assessed in two behaviorally divergent mouse strains and in Long-Evans Rats using an incremental repeated acquisition (IRA) procedure. Animals acquired a novel response sequence (learning condition) or performed a previously acquired sequence (performance condition) during a session. The response sequence increased from a 1- to a 4-response sequence using a mastery-based criterion to increment. A weighted sum of completed (reinforced) sequences provided an excellent measure of progress through the chain. This progress quotient (PQ) and total responding were especially revealing. Significant strain differences in PQ and total responding emerged immediately and persisted for the duration of the study during both the acquisition and performance of sequences. BALB/c mice responded at significantly higher rates and acquired longer sequence-lengths faster and more efficiently than did the C57BL/6 mice. The behavior of BALB/c, but not C57BL/6 mice, during an IRA procedure resembles that of other species, including the rat. This suggests that BALB/c mice are well-suited for complex learning tasks. We hypothesize that the poorer performance of the C57BL/6 mice is due to hyperactivity or habituation and/or satiation to sucrose. |
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| Mouse Models With Short-Term Memory Deficits: The Use of a Titrating Delayed Matching-to-Position Procedure |
| MIRANDA NICOLE REED (University of Minnesota), Karen H Ashe (University of Minnesota), James P. Cleary (University of Minnesota) |
| Abstract: Animal models of human diseases and aging are incredibly useful for understanding the molecular basis of memory loss and cognitive dysfunction, as well as potential therapies. Cognitive dysfunction in transgenic mouse models is often evaluated using the Morris water maze, and while transgenic mice typically show some improvement with repeated testing, they often never reach the same level of performance as controls. In addition, the Morris water maze is considered a stressful event, making it difficult to decipher whether deficits are due to impairments in learning and memory or differences in the perception of stress. To combat these issues, we implemented a titrating delayed matching-to-sample procedure, which allows for the measurement of abilities that are relevant to human aging, has been used with humans, including Alzheimer’s disease patients, and does not require the presentation of aversive or stressful stimuli. Because the use of a fixed delay can result in differences in the frequency of reinforcer presentation, after reaching 80% accuracy with a 3 second delay, the delay length was titrated so that each mouse maintained approximately 80% matching accuracy. Using the Tg2576 Alzheimer’s disease mouse model, we found significant delays in the acquisition of a 3 second delay, and once criterion was met, Tg2576 mice tolerated much shorter delays than transgenic negative mice. Interestingly, this effect was dependent upon which background strain the Tg2576 construct was found. 129/S6 Tg2576 mice exhibited the pattern described above, whereas B6/SJL Tg2576 mice failed to acquire the task even with the implementation of a correction procedure. |
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