Christian Bravo-Rivera, Leonardo J. Ramírez-Sánchez and Bo Li

Reward is often present in risky environments, requiring individuals to weigh the benefits of rewards against the associated risks. There are individuals that are unable to choose an appropriate response during risky reward opportunities and thus exhibit extreme avoidance or risky behaviors that can severely impair quality of life or endanger people. It is therefore necessary to characterize how neurons mediate reward approach and threat avoidance conflict.

Here, we used a novel approach-avoidance conflict task to characterize individual differences in behavior and neuronal activity in mice. Here, we adapted the platform-mediated avoidance conflict task (Bravo-Rivera et al 2014; Bravo-Rivera et al 2021), such that water-deprived mice could nose-poke for a light-signaled water reward (3 uL, 4 sec ITI) and avoid a tone-signaled (20 sec, 70 dB) foot-shock (0.2 mA, 2 sec co-terminating) by stepping onto a safety platform away from the reward port. Mice were trained in two different conflict contingencies; in low conflict, reward was available during safety periods (inter-tone intervals) and during the warning tone, whereas in high conflict, reward was available only during the warning tone. All mice (n = 10 males, 10 females) learned to actively avoid the signaled shock in >90% of trials by the tenth day of low conflict training. Interestingly, females mounted the platform earlier than males after tone onset (5 sec vs 10 sec to reach 80% mount likelihood), and had a longer latency to leave the platform after tone offset (16 sec vs 10 sec to reach 15% mount likelihood) in low conflict. Females also mounted the platform earlier than males after tone onset (15 sec vs 17 sec to reach 80% mount likelihood) in high conflict. Males received more shocks than females (5 vs 2 out of 20) and received more water reward (759 ul vs 609 ul) than females by the end of high conflict training. These results suggest that females exhibit more avoidance behavior and less reward approach than males in the face of approach/avoidance conflict. We then used cFos immunolabeling to characterize neuronal activity profiles of mice exhibiting variable conflict behavior after a high conflict session. This approach will allow us to characterize sex differences in approach/avoidance conflict behavior and the neuronal activity profiles that may underlie those differences.

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