Periodic Reporting for period 1 - ACoDM (Affective Control of Decision Making) Berichtszeitraum: 2019-05-01 bis 2021-04-30 Zusammenfassung vom Kontext und den Gesamtzielen des Projekts In daily life, animals are faced with innumerable decisions as they interact with the environment. Decisions should be made in unfamiliar situations, without a priori knowledge about the potential risks or benefits; or based on previous experience, where the decision is taken evaluating information about known possible outcomes that involve emotional and motivational factors. Moreover, decision making requires the constant re-evaluation of the values linked to those outcomes. Since during these cognitive processes many novel and familiar factors should be combined, compared and contrasted, it is not surprising that numerous neural networks distributed in distinct brain regions contribute to decisions. Thus, decision making requires the interplay of multiple neural structures. Among them the most studied ones are the frontal cortices and the striatum. Much less attention has been focused on the amygdala in spite of recent human studies, suggesting an important role for this brain structure in guiding action-selection processes underlying decisions. As the amygdala is commonly affiliated to emotion and affective behaviour, the value-based decisions can be effectively controlled by amygdalar networks particularly under risky and ambiguous conditions, as suggested by studies in human patients with brain damage or dysfunctions involving the amygdala.The project ACoDM aims to understand affective aspects of circuit mechanisms underlying decision making, with special focus on the circuit conformed by the basal amygdala (BA), the prelimbic cortex (PrL) and the striatum (dorsomedial –DMS- and posterior –pStr-). To this end, three sets of experiments were performed: the first, aimed to differentiate the function of the BA and the pStr in an approach-avoidance conflict; the second, aimed to understand potential behaviours and stimuli that might be affected by the function of striatal neurons; the third, aimed to uncover the mechanism by which the neural activity in the PrL and the DMS is controlled by the BA afferents during a risk-taking decision-making paradigm. The results show that the inhibition of the BA enhances the avoidance behaviour, while the inhibition of the pStr reduces avoidance behaviour. Moreover, the activity of a large portion of pStr neurons (30.26%) is related to a wide range of behavioural responses and they respond to acoustic stimulation (46%), with short latencies. Thus, neural circuits comprising the pStr may be involved in shifting behavioural actions controlled by environmental inputs. Finally, the neurons in the BA show a wide range of responses during the risk-taking decision-making, emphasizing a critical role for the amygdala playing in the processes underlying decisions. Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse The project ACoDM is structured in three main sub-objectives, which have been successfully developed. The first sub-objective elucidates the role of the BA and the pStr in an approach-avoidance conflict. The behavioural task, called active avoidance, confronts thirsty mice with a dilemma, to abandon a safe platform to drink but they take the risk of experience a punishment that is signalled with an auditory cue. Thus, we had two groups of animals one with the brain nucleus of interest inhibited (preventing its normal function) and the other used as controls to know the usual behaviour. We performed this experiment initially to uncover the function of the BA and later of the pStr in the active avoidance. The results show that the inhibition of the BA increases the avoidance behaviour, while the inhibition of the pStr reduced avoidance behaviour. The second sub-objective clarifies potential behaviours and stimuli that might be affected by the function of striatal neurons. We recorded the electrical activity of individual neurons in the pStr, while the mice explored a behavioural box, that was later evaluated or received auditory stimuli (a complex white noise or a pure frequency tone). The results confirm that a large fraction of neurons is activated to specific movement-related behaviours like the exploration. The results also show that the neurons in the pStr change their activity in response to the sound delivery, some neurons respond to the complex white noise, others to the pure frequency tone and a fraction to both of them. Furthermore, the time the acoustic stimuli need to reach the pStr is similar to that of the primary auditory cortex.The third sub-objective uncovers the mechanism by which the neural activity in the PrL and the DMS is controlled by the BA afferents during a risk-taking decision-making paradigm. The behavioural task, called gambling task, confronts thirsty mice with a dilemma, they have to choose between a safe-small reward or a larger reward that might be paired with a punishment (air-puff). At the same time, we recorded the electrical activity of individual neurons in the BA and used optogenetic stimulations to identify PrL- and DMS- projecting neurons. The results show that neurons in the BA change their activity in relation to different aspects of the task, as an example when the mouse receives the reward (more frequent) or receives the punishment. We also identified several light-driven neurons, but analysis is required in order to understand the actual complexity of the proposed network.As for the dissemination, the results from this project have been submitted to four scientific meetings: 18th Meeting of the Spanish Neuroscience Society, KOKI Napok 2019, IBRO Workshop 2020, and 12th FENS Forum 2020; reaching more than 6000 scientists. Furthermore, the results from the study of the mechanism by which the neural activity in the PrL and the DMS is controlled by the BA afferents will be submitted to the 50th annual meeting of the Society for Neuroscience this year. The results were also presented in an outreach activity dedicated to encourage high school students to pursue a scientific career, attended by more than 300 students. The scientific output of this project is one manuscript in preparation based on the aforementioned results. Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts) The ACoDM project has achieved significant advances in our understanding of the circuits conformed by the basal amygdala, the prelimbic cortex and the striatum (dorsomedial and posterior) and how they contribute to decision-making. The BA and pStr seem to play opposing roles in the performed active avoidance paradigm, which implies that the balance in the activity of these nuclei might be related to aberrant decision-making. In addition, the pStr, as it receives direct auditory input, might mediate auditory-based action selection and this process might be parallel to the processing of auditory information in the primary auditory cortex. The neuronal activity in the BA during a risk-taking task shows a wide range of responses, emphasizing a critical role it has in the processes underlying decisions. Overall, the ACoDM project significantly advances our current understanding about decision-making and the role of the amygdala in this process. The project ACoDM, affective aspects of the circuit mechanisms underlying decision making.