Neuronal circuits underlying cooperative behaviors between rodents

Resumen

-------- Abstract Social behaviors such as cooperation are crucial for the life of mammals, including humans. A better knowledge of the neuronal mechanisms underlying cooperative behaviors can have a positive impact on the quality of life of people suffering from pathologies in which social behavior is impaired, such as autism and schizophrenia. In this Doctoral Thesis, we examined the electrical properties and mechanisms in three selected brain structures during an instrumental cooperative task in rats. Specifically, we examined the prelimbic cortex (PrL), the nucleus accumbens septi (NAc) and the basolateral amygdala (BLA), three brain sites that were previously linked to social behaviors. To study the functional changes in the activity of these structures during cooperation, we developed a double Skinner box divided by a metallic grille, which allowed a pair of rats to see and smell each other and have limited physical contact through the grille. Once the apparatus was developed, we designed a protocol for the acquisition of an instrumental cooperative task. First, rats were trained to individually climb onto a platform to obtain a food reward. After that, rats were progressively trained to climb on their respective platforms (and stay there simultaneously for > 0.5 s) to get food pellets for both animals. This set-up was compatible with the in vivo recording of local field potentials (LFPs) at the places of interest during the acquisition of the cooperative task. To the best of our knowledge, this was a pioneer study on brain mechanisms underlying cooperative behaviors between mammals. With the designed apparatus and protocol, rats were capable of synchronizing their behaviors and adjusting their responses to cooperate for a mutual reward in three different experiments: In the first experiment, we studied the implication of the PrL cortex during the cooperation task. In general, the PrL activity increased when rats were on the platform compared with periods off the platform. Rats also showed a clear differentiated role during the cooperating phase. Some rats (designated leaders) adjusted their behavior to their partners to cooperate, while other rats (designated followers) kept an individual strategy. These behavioral changes correlated with changes in the spectral power of the LFPs recorded in the PrL cortex, with the highest power observed in the delta frequency band for leader rats during the cooperation task. In the second experiment, four groups of rats performed the cooperation protocol, without electrodes this time, and their brains were collected at key moments of the learning process (for example, after reaching the criterion for the cooperative phase). The aim was to analyze the levels of cFOS expression in the main cellular subgroups inside the PrL cortex across the different phases. In this experiment, rats completed the cooperation task successfully and there was also a difference in the roles that rats developed during cooperation: leaders or followers. Leader rats showed increased cFOS expression in dopaminergic cells expressing D1 receptors during the cooperation phase in comparison with follower rats and the individual phase. In the last experiment, we studied the implication and functional connectivity of the PrL cortex, the NAc and the BLA during the cooperation task. As in the first experiment, the PrL activity increased when rats were cooperating on the platform, this time compared to PrL activity seconds before climbing to the platform. The same occurred with the activity recorded in the NAc, while BLA activity in delta and theta bands decreased considerably when rats were cooperating on the platform. PrL and NAc increased their high theta band connectivity when rats were cooperating on the platform while the connectivity in the delta and low theta bands decreased. The functional connectivity between NAc and BLA decreased in delta and theta bands when rats were cooperating on the platform.