Quantifying Social Motivation in Mice Using Operant Conditioning

The overall goal of this procedure is to quantify social motivation and laboratory mice. This is accomplished by first training each test mouse to associate lever pressing with a social reward. The second step is to test each mouse in a series of sessions in which the amount of effort required to obtain the social reward increases across trials.

Next, each test mouse is trained to discriminate between two lever and reward contingencies. The final step is to test each mouse in a series of sessions in which they can choose between these contingencies resulting in either a social or food reward. Ultimately, these opera social motivation paradigms allow investigators to quantify social motivation and compare this level to that of a food reward.

The main advantage of this technique over existing methods is that this paradigm requires progressively more effort to obtain a social reward than tasks. Simply measuring time spent in proximity to a social partner Demonstrating the procedure will be Brianna Lum, Megan Raymond, Amy Patterson, and Maryanne Slamma undergraduate student researchers in my laboratory. To begin set up center channel modular shuttle boxes for use in testing social behavior, mount a wire grid to the face of a programmable guillotine door to separate the chambers and allow limited social contact between them.

The door divides the box into two chambers, designate one chamber as a test chamber, and the other as a target chamber on the wall opposite to the door. Place a liquid dipper food receptacle between the two mice levers program. The mouse levers to either open the guillotine door or present a liquid food reward.

Depending on testing requirements, program a handheld button to open the door when pressed. During the shaping procedure, monitor activity of the test mice Using a digital video camera mounted above the test chamber. The entire apparatus is enclosed in a sound attenuating cubicle.

Begin by placing the test mouse in the test chamber and an age and sex match stimulus mouse in the target target chamber. Observe the test mouse in the test chamber using the mounted video camera. As the test mouse explores the chamber manually trigger the guillotine door to open.

When the lever is approached, allow the guillotine door to remain open for 15 seconds of reinforcement. Train each mouse for 30 minutes a day until they demonstrate at least 10 operant responses in three out of five consecutive testing sessions. Remove mice from the study if they do not reach this criterion after 30 daily training sessions.

Alternate the stimulus mice used during shaping so that a different mouse is used every day. Clean the shuttle boxes between each training session using 70%ethyl alcohol. Additionally, clean all equipment using a disinfecting detergent at the end of the testing day.

During testing, use a pool of novel stimulus mice large enough so that they are not repeated during 10 daily test sessions. To begin, place a trained test mouse in the test chamber and a stimulus mouse in the target chamber. Program the door to open such that the number of lever presses needed to obtain the social reward increases by a fixed rate of three each trial.

End the session when the test mouse stops. Lever pressing for five consecutive minutes. Record the last reinforced ratio as the break point.

Test each mouse for 20 consecutive daily sessions or for at least 10 test sessions. After asymptotic performance levels are observed. Wipe down shuttle boxes between each testing session as demonstrated earlier after testing in the social motivation paradigm, the same mice are trained in a task that includes a food reward.

Prepare evaporated milk sweetened with 0.2%sucrose to use as a liquid food reward. Next program, one lever to open the door and the other to present the liquid food reward. Alternate the reward presentation.

To avoid introducing a lever bias in the test mice begin by placing mice in the respective chambers. Only one lever and reward presentation should be active during each session. Training consists of six one hour sessions that alternate between contingencies each day during testing program the schedule of reinforcement at a fixed ratio of three to one so that every third lever presses on each side is reinforced.

Continue testing for 60 minutes a day for 20 days, or at least 10 daily sessions following the observation of asymptotic performance levels. Clean the shuttle boxes as shown earlier. The mean breakpoint of individually housed B six mice was similar to that of group housed B six mice while grouped housed BTBR mice showed a significantly lower breakpoint.

BTBR mice acquired significantly fewer food rewards compared to B six mice. While both groups obtained more food rewards than social rewards. These results show the difference in performance across the genotypes of a transgenic mouse line.

An additional study involving a different transgenic mouse line shows heterozygous mice having a higher breakpoint when compared to wild type siblings In conjunction with this procedure. Other methods such as video monitoring of the test and stimulus mice can be employed in order to answer additional questions such as what specific social behaviors are exhibited during the presentation of the social reward. After watching this video, you should have a good understanding of how to use operant conditioning to quantify social motivation in laboratory mice.

This procedure can be especially useful for phenotyping mouse models of autism and other disorders of social behavior.