Nautiyal, K. M. | bioRxiv Science

bioRxiv2020

DIY-NAMIC behavior: A high-throughput method to measure complex phenotypes in the homecage

Complex behavioral assessment is becoming increasingly necessary in order to comprehensively assess in vivo manipulations in rodent models. Using operant behavioral paradigms provides rich data sets allowing for the careful analysis of behavioral phenotypes. However, one major limitation in these studies is the expense and work-load that are required using traditional methods. The equipment for commercial operant boxes can be prohibitively expensive, and the daily experimenter effort and mouse costs required for these studies is extensive. Rodents are generally trained on task-specific paradigms for months, tested every day for 5-7 days per week. Additionally, appetitive paradigms usually require food restriction and are also commonly run in the non-active light phase of the rodent circadian rhythm. These limitations make operant behavioral testing especially difficult during adolescence, a time period of interest with regards to the development of adult-like phenotypes and a high-risk period for the development of neuropsychiatric disorders, including those which involve impulsive behavior. In order to address these issues, we developed an automated, inexpensive, open-source method which allows the implementation of most standard operant paradigms in the homecage of rodents in shorter time frames without food restriction, and with much less experimenter effort. All construction and code for the DIY Nautiyal Automated Modular Instrumental Conditioning (DIY-NAMIC) system are open source. We demonstrate their utility here by measuring impulsive behavior in a pharmacology experiment, as well as in adolescent mice.Significance statement Rigorous behavioral assessment is critical to understand the neural basis of neuropsychiatric disorders using animal models. Operant behavioral paradigms provide the ability to measure complex phenotypes, however, traditional methods generally require time-consuming daily training for many weeks. We designed, built, and tested an open-source automated homecage system for appetitive instrumental conditioning that enables testing in shorter timeframes with reduced experimenter effort.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2020

A role for reward sensitivity in the serotonergic modulation of impulsivity

Impulsive behavior is a deleterious component of a number of mental health disorders but has few targeted pharmacotherapies. One contributing factor to the difficulty in understanding the neural substrates of disordered impulsivity is the diverse presentations of impulsive behavior. Defining the behavioral and cognitive processes which contribute to different subtypes of impulsivity is integral to understanding and treating disorders with dysregulated impulsive behavior. Our approach was to first determine what behavioral and cognitive phenotypes are associated with increased impulsive behavior, and then probe if they could causally contribute to increasing impulsivity. We used a mouse model for disordered impulsivity - mice lacking the serotonin 1B receptor (5-HT1BR) which have deficits specific to impulsive action, and not other components of impulsive behavior. Here we report, that in addition to increased impulsive action, mice lacking expression of 5-HT1BR also have increased goal-directed responding and motivation, with no differences in extinction, development of habitual behavior, delay discounting, or effort-based discounting. Interestingly, mice lacking 5-HT1BR expression did show an overall increase in the choice of higher value rewards, increased hedonic responses to sweet rewards, and responded more to cues that predict reward, compared to controls. We developed a novel paradigm to demonstrate that increasing anticipated reward value could directly increase impulsive action. Furthermore, we found that 5-HT1BR KO-induced impulsivity could be ameliorated by decreasing the reward value relative to controls, suggesting that the increased 5-HT1BR-associated impulsive action is a result of increased reward valuation. Taken together, these data show that the effects of serotonin on impulsive action are mediated through the modulation of hedonic value, which may alter the reward representations that motivate action. Additionally this work supports a role for reward valuation as an important substrate in impulsive action which may drive clinically-relevant increases in impulsivity.

neuroscience↗