CORDIS - EU research results

Circuit mechanisms of fear vs. reward in the limbic system

Final Report Summary - FEARREWARDCIRCUITS (Circuit mechanisms of fear vs. reward in the limbic system)

The main objective of the project is to investigate how opposite emotional states, like fear and reward, are differentially processed in the brain. We hypothesize that these basic emotions are encoded by interactions of neural circuits specific for negative or positive emotional valence and circuits for arousal (independent of valence).
We first developed a new behavioural paradigm to induce positive and negative emotional states in the same animals. Mice first learn a Pavlovian reward conditioning task, during which an auditory conditioned stimulus (reward-CS) is always followed by a rewarding sucrose delivery inside the port of the experimental chamber. After successful learning, mice undergo a Pavlovian fear conditioning protocol during which a different sound (fear-CS) is paired with an electric footshock. During test sessions without reward or shock delivery, mice expressed the correct emotional response, i.e. freezing (immobility indicating fear) only during fear-CS and port visits (indicating reward-seeking) selectively during reward-CS.
We found that the arousal level increases similarly during fear and reward states in our paradigm, by quantifying the plasma level of corticosterone, a hormone indicator of physiological arousal. By performing a global brain mapping, we also found that one brain region probably critical for arousal, the bed nucleus of stria terminalis (BNST), as it appeared to be highly activated after both fear-CS and reward-CS. When BNST is inactivated, both fear and reward states decreased, confirming that BNST is involved in both fear and reward emotional states.
The BNST is known to receive major inputs from the basolateral amygdala (BLA), another core brain region for emotions. We thus examined the effect of manipulating the activity of BLA-to-BNST, by using optogenetic approaches, on the expression of fear and reward. We found that activation of this circuit decreased both fear and reward expression. This finding suggests that this BLA-to-BNST circuit may be involved in encoding arousal.
Finally, we aim to identify cellular and genetic features specific for “positive valence”, “negative valence” and “arousal” neurons in BNST and amygdala. For this purpose, we are using a fluorescent protein called “timer”, which changes its colour - from blue to red - over time after cellular activation. We observed in transgenic mice neurons that are red, blue or both in response to a rewarding and a negative stimulus. With this tool, we aim to identify neuronal populations activated by fear-CS and reward-CS presented to the same animal at two different time points.
Overall, with this project we expect to provide a detailed mechanism of fear and reward encoding within the amygdala-BNST circuits.